In this study we examined the effect of a dopamine (DA) precursor (L-DOPA) or a serotonin (5-HT) antagonist (Ritanserin) on time to exhaustion. The study had a double-blind, randomised, placebo controlled and cross-over design. Seven moderately trained men performed three tests to exhaustion at 65% Wattmax. Each test was separated by two weeks to allow washout of the drugs (dose: 4 mg/kg Sinemet, and 0.3 mg/kg Ritanserin). Blood lactate, hematocrit, glucose, ammonia, free fatty acids (FFA), growth hormone (GH) and catecholamines were determined before and after exercise. Time to exhaustion did not differ between the three trials. Most of the parameters measured in this study responded as predicted during cycling to exhaustion in man. DA agonism significantly increased heart rate, lactate, and plasma DA values at rest, while other parameters such as FFA, lactate, plasma noradrenaline (NA) and adrenaline (A), and plasma GH showed the highest absolute levels at exhaustion. Ritanserin did not influence basal glucose and heart rate at rest, but this group showed a much lower increase in plasma catecholamine levels. We conclude that under the present conditions, neither a metabolic precursor of DA nor a specific centrally acting 5-HT2A/2C antagonist, when given in two single doses 24 h and immediately before the experiments, influences the time to exhaustion on a bicycle trial at 65% Wattmax.