Human growth hormone (hGH) characteristically increases during physical exercise. In sports medicine, hGH changes have mostly been described in short-term performances under standardized laboratory procedures. We studied hGH and insulin-like growth factor I (IGF-I) under field conditions in 7 runners performing a marathon at 4000 m of altitude, to study the hormonal changes under extreme endurance effort and to evaluate the release of 22 kDa and 20 kDa monomers under these conditions, in comparison with a control group. The blood samples were taken at sea level, after 1 week of acclimatization, immediately after the run, and after a recovery of 24 h from the marathon. hGH was quantified by using a polyclonal method, a 22 kDa specific monoclonal method and a monoclonal method recognizing both 22 kDa and 20 kDa isoforms. A significant increase in hGH was noted using all methods after the marathon, followed by a significant decrease after recovery. Significant differences between athletes and controls were found only for the measurement after the marathon. No statistically reliable decrease of IGF-I was observed in athletes and controls. We obtained more limited hGH rises than previously described in athletes; the importance of lactate levels indicates that the use of physical exercise as a stimulation test for hGH should be closely standardized. The 20 kDa monomer and other hGH molecular forms played a limited role in the hormone increase: in our experience, elevation of hGH in heavy exercise corresponds mostly to the 22 kDa isoform. We suggest that the evaluation of hGH elevation in sports medicine could be accurately performed using specific 22 kDa monoclonal assays.