To examine the effect of intensive aerobic exercise on the interaction between endocrine and immune systems, we studied in ten normal healthy male subjects the effect of a 50-mile walking race on blood concentration of hormones (insulin, GH, ACTH, cortisol, adrenaline, noradrenaline, and dopamine), ketone bodies, specific immunological functions (IgG, IgM, and PHA/Con A-induced lymphocyte blastformation test), and nonspecific immune (CH50, and neutrophil bactericidal functions). Neutrophil bactericidal activity was measured as chemiluminescences amplified by luciferin analog (CLA-DCL) and luminol (L-DCL). The race increased cortisol and ketone bodies, and decreased insulin, CLA-DCL, and L-DCL (all parameters; P < 0.01). However, other parameters were not significantly changed. There were significant negative correlations between changes of ketone bodies/cortisol and CLA/L-DCL (P < 0.05), however there was no significant correlations between changes of insulin and CLA/L-DCL. These data indicate that extensive aerobic exercise causes impaired neutrophil bactericidal function, probably due to the induced increases in both cortisol and ketone bodies. This impaired neutrophil function may cause the susceptibility to infection after an extensive exercise.