A common issue in PCR amplification, especially from complex genomes, is the appearance of spurious smaller bands, often due to mispriming. These spurious products can dominate the reaction and are more likely when target templates are present in small amounts. Adjustments to Mg²+ concentration or annealing temperature may help, but are time-consuming. The authors propose a "touchdown" PCR method, which starts at or above the expected annealing temperature and gradually decreases it over cycles. This approach exploits the exponential nature of PCR, giving the correct product a competitive advantage. A 5°C difference results in a 1024-fold advantage. The method was tested on amplifying cDNA for leukemia inhibitory factor (LIF), where traditional methods produced spurious bands. Using touchdown PCR, sufficient correct-length LIF cDNA was amplified for cloning. A secondary band was also observed, possibly due to internal priming. The touchdown approach is applicable to various situations, bypassing spurious amplifications without lengthy optimization. Even when a suitable temperature is empirically determined, touchdown can help avoid secondary issues like inconsistent temperatures in thermal cyclers. The study was supported by Australian National Health and Medical Research Council grants. Figure 1 shows the results of different PCR conditions, including size standards and controls.A common issue in PCR amplification, especially from complex genomes, is the appearance of spurious smaller bands, often due to mispriming. These spurious products can dominate the reaction and are more likely when target templates are present in small amounts. Adjustments to Mg²+ concentration or annealing temperature may help, but are time-consuming. The authors propose a "touchdown" PCR method, which starts at or above the expected annealing temperature and gradually decreases it over cycles. This approach exploits the exponential nature of PCR, giving the correct product a competitive advantage. A 5°C difference results in a 1024-fold advantage. The method was tested on amplifying cDNA for leukemia inhibitory factor (LIF), where traditional methods produced spurious bands. Using touchdown PCR, sufficient correct-length LIF cDNA was amplified for cloning. A secondary band was also observed, possibly due to internal priming. The touchdown approach is applicable to various situations, bypassing spurious amplifications without lengthy optimization. Even when a suitable temperature is empirically determined, touchdown can help avoid secondary issues like inconsistent temperatures in thermal cyclers. The study was supported by Australian National Health and Medical Research Council grants. Figure 1 shows the results of different PCR conditions, including size standards and controls.