The lateral habenula (LH) is a key source of negative reward signals in dopamine neurons, as shown in a study on rhesus monkeys. Midbrain dopamine neurons are central to the brain's reward system, guiding reward-seeking behaviors. While dopamine neurons respond to rewards and reward-predicting stimuli, the brain regions providing signals for these actions remain unclear. This study demonstrates that the LH, part of the epithalamus, is a major source of negative reward-related signals in dopamine neurons. During a visually guided saccade task with positionally biased reward outcomes, LH neurons were excited by no-reward-predicting targets and inhibited by reward-predicting targets, while dopamine neurons showed the opposite pattern. When reward and non-reward positions were reversed, both LH and dopamine neurons reversed their responses. In unrewarded trials, LH neurons showed earlier excitation than dopamine neurons' inhibition. Electrical stimulation of the LH strongly inhibited dopamine neurons, suggesting that LH's inhibitory input plays a crucial role in determining dopamine neurons' reward-related activity. Dopamine neurons in the substantia nigra pars compacta (SNc) respond to rewards or stimuli predicting rewards, with positive or negative responses based on reward value. The LH, known to project to the SNc and inhibit dopamine neurons, was investigated for its role in reward processing. In the reward-biased visual saccade task, LH neurons showed post-target responses influenced by reward contingency, with stronger responses in unrewarded trials. Dopamine neurons also showed similar post-target responses, but in the opposite direction. After reversing the position-reward contingency, LH and dopamine neurons showed opposite changes in post-target responses. LH neurons' responses increased rapidly after a reward-to-no-reward transition, while dopamine neurons' responses decreased. These findings suggest that LH neurons encode reward prediction errors, similar to dopamine neurons. Electrical stimulation of the LH inhibited dopamine neurons, supporting a causal relationship between LH and dopamine activity. The study highlights the LH's role in negative reward processing, contrasting with dopamine neurons' role in positive reward processing. This aligns with opponent-process theories, where aversive and appetitive systems interact. The LH's inhibitory input to dopamine neurons may underlie the phasic inhibition of dopamine neurons in response to no-reward-predicting targets. The LH's role in motivational control of saccadic eye movements is also suggested, as its activity influences saccade latency. The study provides evidence that the LH is crucial for negative reward processing, with dopamine neurons involved in positive reward processing. The LH's inhibitory input to dopamine neurons may be essential for reward-related activity. The findings suggest that the LH plays a pivotal role in integrating reward information, with inputs from limbic areas and interactions with the basal ganglia and monoaminergic systems. The study's results support the hypothesis that the LH is a key component of the brain's reward system, providing negative reward signals to dopamine neurons.The lateral habenula (LH) is a key source of negative reward signals in dopamine neurons, as shown in a study on rhesus monkeys. Midbrain dopamine neurons are central to the brain's reward system, guiding reward-seeking behaviors. While dopamine neurons respond to rewards and reward-predicting stimuli, the brain regions providing signals for these actions remain unclear. This study demonstrates that the LH, part of the epithalamus, is a major source of negative reward-related signals in dopamine neurons. During a visually guided saccade task with positionally biased reward outcomes, LH neurons were excited by no-reward-predicting targets and inhibited by reward-predicting targets, while dopamine neurons showed the opposite pattern. When reward and non-reward positions were reversed, both LH and dopamine neurons reversed their responses. In unrewarded trials, LH neurons showed earlier excitation than dopamine neurons' inhibition. Electrical stimulation of the LH strongly inhibited dopamine neurons, suggesting that LH's inhibitory input plays a crucial role in determining dopamine neurons' reward-related activity. Dopamine neurons in the substantia nigra pars compacta (SNc) respond to rewards or stimuli predicting rewards, with positive or negative responses based on reward value. The LH, known to project to the SNc and inhibit dopamine neurons, was investigated for its role in reward processing. In the reward-biased visual saccade task, LH neurons showed post-target responses influenced by reward contingency, with stronger responses in unrewarded trials. Dopamine neurons also showed similar post-target responses, but in the opposite direction. After reversing the position-reward contingency, LH and dopamine neurons showed opposite changes in post-target responses. LH neurons' responses increased rapidly after a reward-to-no-reward transition, while dopamine neurons' responses decreased. These findings suggest that LH neurons encode reward prediction errors, similar to dopamine neurons. Electrical stimulation of the LH inhibited dopamine neurons, supporting a causal relationship between LH and dopamine activity. The study highlights the LH's role in negative reward processing, contrasting with dopamine neurons' role in positive reward processing. This aligns with opponent-process theories, where aversive and appetitive systems interact. The LH's inhibitory input to dopamine neurons may underlie the phasic inhibition of dopamine neurons in response to no-reward-predicting targets. The LH's role in motivational control of saccadic eye movements is also suggested, as its activity influences saccade latency. The study provides evidence that the LH is crucial for negative reward processing, with dopamine neurons involved in positive reward processing. The LH's inhibitory input to dopamine neurons may be essential for reward-related activity. The findings suggest that the LH plays a pivotal role in integrating reward information, with inputs from limbic areas and interactions with the basal ganglia and monoaminergic systems. The study's results support the hypothesis that the LH is a key component of the brain's reward system, providing negative reward signals to dopamine neurons.