The present study was undertaken to examine the effect of a high carbohydrate diet on the functional activity of 5-HT1B/1D receptors in human peripheral blood lymphocytes, and on serum cortisol and plasma cytokine responses during intense military training. Thirty two male soldiers (mean age: 21 +/- 2 years) were randomly assigned to two groups and received either 3200 kcal/24 h [13440 kJ; habitual diet group (HD)] or 4200 kcal/24 h [17640 kJ, high carbohydrate diet group (HCD)] by adding 1000 kcal (4200 kJ) of fruit jelly to the HD. They took part in a three-week training program followed by a five-day combat course. Blood samples were collected from each group before entry into the commando training and after the five-day combat course. The results of [35S] GTPgammaS binding assays showed that h5-HT1B/1D receptors were desensitized after the training program in the HD group, whereas no change was observed between the beginning and the end of the military training in the HCD group [(HD : IC50 = 100 +/- 14 nM to 544 +/- 178 nM; n = 16) and (HCD: IC50 = 68 +/- 14 nM to 101 +/- 22 nM; n = 16)]. Serum cortisol was only significantly increased after the commando training in the HD group (from 532.2 +/- 30 to 642 +/- 45 nmol.L(-1), p < 0.05), whereas values were not significantly changed in the HCD group (441 +/- 31 to 502 +/- 40 nmol.L(-1)). No changes were observed in IL-10, TNF-alpha and IFN-gamma levels after the training program in either group. Carbohydrate ingestion or additional dietary energy during repeated bouts of high-intensity exercise could attenuate the alterations in immune function via 5-HT1B/1D receptors and the action of 5-HT moduline, an endogenous tetrapeptide (Leu-Ser-Ala-Leu) that specifically modulates the sensitivity of 5-HT1B/1D receptors.