The effect of carbohydrate (CHO) ingestion on antigen- (rather than mitogen-) stimulated T cell responses to prolonged, intensive exercise may give a more realistic insight into the effect of CHO on T cell functional capacity and subsequent infection risk. This study investigated the effect of CHO ingestion during prolonged, intensive exercise on influenza- and tetanus toxoid-stimulated T cell cytokine mRNA expression and proliferation. Mitogen- (PHA) stimulated proliferation was assessed for comparison. Responses were assessed following exercise on consecutive mornings to determine any 'carry-over' effect. Fifteen male games players performed two exercise trials in a double-blind randomised crossover design. Each trial comprised 90 min of intensive intermittent running on consecutive mornings, with either CHO (6.4% w/v) or placebo (PLA) beverage ingestion before, during and after each bout of exercise. Post-exercise CD3+ cell counts were higher in PLA than CHO on both days (P<0.05). Antigen-stimulated T cell cytokine mRNA expression was unaffected by exercise or CHO ingestion. Before exercise on day 2, T cell proliferative responses to PHA, influenza and tetanus toxoid were higher in CHO than PLA by 99%, 80% and 58%, respectively (P<0.01 for PHA, P<0.05 for influenza and tetanus toxoid). At 1 h post-exercise on day 2, PHA-induced proliferation was 70% higher in CHO than PLA (P<0.05) yet there were no differences between trials for antigen-induced proliferative responses. Therefore, mitogen-induced T cell proliferation following strenuous exercise and CHO does not necessarily reflect responses to specific antigens and consequently may not provide a good model for the situation in vivo.