Central catecholamines influence attention, arousal, motivation and motor control. Bupropion, a dual noradrenaline/dopamine reuptake inhibitor, improves time trial performance in male subjects in the heat (Watson et al. 2005). Gender differences in neuropsychopharmacology have been shown in animal and human studies (Young & Becker 2009), but it is not known whether these differences may alter the effect of Bupropion on exercise performance in women. With local ethics committee approval, 9 habitually physically active women (Mean ± SD age 21±2 y; height 1.68±0.08 m; body mass 64.1 ±6.0 kg; VO2max 50.9±7.2 ml/kg/min) were recruited to examine the effect of pre-exercise administration of Bupropion (4×150 mg) on prolonged exercise performance in a warm environment (30.2±0.2°C, 50%±1% rh). Subjects completed a VO2max test, a familiarisation trial, and a single-blinded placebo control trial before a randomised, double-blind, placebo-controlled crossover design was employed. Experimental trials took place during the first 10 days of the follicular phase of the menstrual cycle. Subjects cycled for 1 h at 60% VO2max followed by a 30 min workload challenge, during which they completed as much work as possible. Heart rate, skin and core temperature, and ratings of perceived exertion and thermal comfort were recorded throughout exercise. Data were analysed with repeated measures ANOVA. Pairwise comparisons were made with LSD where appropriate and Bonferroni’s test for multiple comparisons. Total work done was higher on the Buproprion trial (291±48 kJ) than on the single-blind (267±48 kJ, P=0.021) and double-blind trials (269±46 kJ, P=0.042). No differences were found between all trials for core temperature throughout rest, the first hour or the workload challenge. However, at the end of the workload challenge core temperature was higher on the Bupropion trial (39.5±0.4 °C) than the single-blind (39.2±0.6 °C, P=0.028) and double-blind trials (39.2±0.6 °C, P=0.021). Heart rate was also higher at the end of the workload challenge on the Bupropion trial (185±9 bpm) than the single-blind (180±13 bpm, P=0.048) and double-blind trials (179±13 bpm, P=0.043). The results indicate that during the follicular phase of the menstrual cycle an acute dosing protocol of Bupropion can improve self-regulated work rate in warm conditions.