The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Growth factors and serum inhibit programmed cell death (apoptosis) and promote cell survival. The study investigated five downstream effectors of growth factor receptors—Ras, Raf, Src, PI 3-kinase, and Akt (PKB)—to determine their ability to block apoptosis. Activated forms of Ras, Raf, and Src, although transforming, were not sufficient to deliver a survival signal upon serum withdrawal. In contrast, inhibition of PI 3-kinase accelerated apoptosis, and an activated form of Akt, a downstream effector of PI 3-kinase, blocked apoptosis. The ability of Akt to promote survival was dependent on and proportional to its kinase activity. In Rat1a fibroblasts, activated Akt did not alter Bcl-2 or Bcl-XL expression but inhibited Ced3/ICE-like activity. Thus, the PI 3-kinase/Akt signaling pathway transduces a survival signal that ultimately blocks Ced3/ICE-like activity. These results suggest that uncoupling of survival and mitogenesis can be explained by differing abilities of distinct mitogens to efficiently induce the PI 3-kinase/Akt signaling pathway. The study also showed that Akt does not elevate Bcl-2 or Bcl-XL expression but inhibits PARP protease activity upon serum withdrawal. Akt's ability to promote survival is dependent on its kinase activity. The PI 3-kinase/Akt pathway is crucial for cell survival and may have a broader role in embryonic development and longevity of adult tissues. The study highlights the importance of the PI 3-kinase/Akt pathway in mediating survival signals and its potential as a target for cancer therapy.The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Growth factors and serum inhibit programmed cell death (apoptosis) and promote cell survival. The study investigated five downstream effectors of growth factor receptors—Ras, Raf, Src, PI 3-kinase, and Akt (PKB)—to determine their ability to block apoptosis. Activated forms of Ras, Raf, and Src, although transforming, were not sufficient to deliver a survival signal upon serum withdrawal. In contrast, inhibition of PI 3-kinase accelerated apoptosis, and an activated form of Akt, a downstream effector of PI 3-kinase, blocked apoptosis. The ability of Akt to promote survival was dependent on and proportional to its kinase activity. In Rat1a fibroblasts, activated Akt did not alter Bcl-2 or Bcl-XL expression but inhibited Ced3/ICE-like activity. Thus, the PI 3-kinase/Akt signaling pathway transduces a survival signal that ultimately blocks Ced3/ICE-like activity. These results suggest that uncoupling of survival and mitogenesis can be explained by differing abilities of distinct mitogens to efficiently induce the PI 3-kinase/Akt signaling pathway. The study also showed that Akt does not elevate Bcl-2 or Bcl-XL expression but inhibits PARP protease activity upon serum withdrawal. Akt's ability to promote survival is dependent on its kinase activity. The PI 3-kinase/Akt pathway is crucial for cell survival and may have a broader role in embryonic development and longevity of adult tissues. The study highlights the importance of the PI 3-kinase/Akt pathway in mediating survival signals and its potential as a target for cancer therapy.