The influence of medroxyprogesterone acetate (MPA) on exercise performance was studied in a double-blind cross-over trial using six normal males to compare the exercise performance changes to those observed in a previous study of exercise responses of female subjects during the follicular and luteal phase of the menstrual cycle. A maximal progressive work exercise test on a cycle ergometer was performed after 2 weeks of placebo or MPA administration. Although five of six subjects spontaneously complained of increased exertional dyspnoea on MPA, no significant decreases were documented in maximal exercise time or in maximal oxygen consumption. A mean increase in exercise ventilation of 19% at low levels of exertion and 26% at high levels of exertion was documented, but no subject demonstrated evidence of ventilatory limitation. The increases in exercise ventilation observed in these male subjects after MPA administration were larger than those observed in the previous study comparing exercise ventilatory responses during follicular and luteal phases of the menstrual cycle. It seems possible that some other exercise-related modulator of the ventilatory response to exercise under the influence of progesterone is present in either male subjects receiving MPA or women with normal hormonal cycles.