BACKGROUND: Proposed differences in caffeine metabolism due to the CYP1A2*1F polymorphism have been linked to variations in cardiovascular disease risk. AIMS: We examined the influence of a CYP1A2*1F polymorphism on post-exercise heart rate variability (HRV) in response to caffeine intake. METHODS: Volunteers were identified as A/A homozygotes (A/A; 4 females and 7 males; age: 25.3 +/- 4.1 years; BMI: 25.9 +/- 4.4 kg/m(2)) or C allele carriers (C allele; 3 females and 6 males; age: 25.5 +/- 2.8 years; BMI: 26.6 +/- 5.0 kg/m(2)) for participation in a repeated measures, counterbalanced, double-blind, placebo-controlled trial. Participants chewed three pieces of gum containing either caffeine (CAF) (100 mg/piece) or placebo for 5 min. Thereafter, participants cycled for 15 min at 75 % of their peak oxygen consumption. Eight HRV indices computed during 5 min at baseline (BASE), 0-5 min after exercise (POST1), and 5-10 min after exercise (POST2) were used for analysis. RESULTS: No significant group differences were detected in HRV indices at BASE, POST1, or POST2 during both trials (p > 0.05). Rate of recovery (POST2-POST1) for the square root of the mean of squared differences between successive RR intervals (RMSSD) was significantly different between A/A (6.0 +/- 2.5 ms) and C allele (3.6 +/- 2.5 ms) groups during the CAF trial (p = 0.048). CONCLUSIONS: Rate of RMSSD recovery was the only variable influenced by the CYP1A2*IF polymorphism during post-exercise in response to caffeine intake. Thus, the CYP1A2*1F polymorphism did not overtly influence the effects of caffeine intake on post-exercise HRV.