AIM: The aim of this study was to compare the activity of the autonomic nervous system (ANS) using heart rate variability (HRV) in \'healthy\' young smokers and non-smokers before, during and after exogenous hypoxic provocation. METHODS: Twenty-one healthy non-smoking males aged 28.0 +/- 7.4 years (mean +/- SD) and 14 \'healthy\' smoking males aged 28.1 +/- 4.3 years with 9.2 +/- 5.6 pack-years were subjected to one-hour hypoxic exposure (F(i)O(2) = 12.3 +/- 1.5%) via a hypoxicator. HRV data was derived via Kubios HRV, Finland software by analysing the pre-hypoxic, hypoxic and post-hypoxic periods. RESULTS: Standard deviation of the intervals between normal beats (SDNN) was higher in the non-smokers in the pre-hypoxic period (62.0 +/- 32.1 vs 40.3 +/- 16.2 ms, p = 0.013) but not in the hypoxic period (75.7 +/- 34.8 vs 57.9 +/- 18.3 ms, p = 0.167). When comparing intra-group HRV changes, shifting from hypoxic to normoxic conditions, there was an increase in the mean square root of successive R-R interval differences (RMSSD) (65.9 +/- 40.2 vs 75.1 +/- 45.9 ms, p = 0.011), but these changes were observed in only the group of non-smokers. CONCLUSIONS: Smoking probably impairs autonomic regulation in healthy young males and may lead to decreased HRV, even before subjective clinical signs and symptoms appear.