To examine the effect of exercise and heat stress on cytokine production, seven males (77 +/- 2 kg; VO(2peak) = 4.7 +/- 0.4 L min(-1)) completed two (15 degrees C; CON or 35 degrees C; HEAT) 90 min cycling trials at 70% VO(2peak). Blood samples were collected throughout and analysed for spontaneous, and LPS-stimulated intracellular monocyte cytokine production, plasma cytokine levels, and circulating stress hormone concentration. Plasma epinephrine, norepinephrine, and cortisol concentration were elevated (P < .05) as a result of exercise in CON. HEAT increased (P < .05) epinephrine and norepinephrine levels, however, cortisol concentration was not different between the two trials. Exercise had no effect on the concentration of circulating monocytes spontaneously producing IL-6, TNF-alpha or IL-1alpha, however, there was a decrease in the amount of TNF-alpha per cell post-compared with pre-exercise. HEAT had no effect on spontaneous intracellular cytokine production. Circulating levels of both IL-6 and TNF-alpha were elevated in HEAT, but not in CON. Upon stimulation with LPS, the concentration of monocytes positive for IL-6, TNF-alpha, and IL-1alpha production was elevated (P < .01) post- and 2 h post-compared with pre-exercise. Stimulated cells, however, produced less (P < .05) TNF-alpha post-exercise and less (P < .05) TNF-alpha and IL-6 2 h post-exercise. HEAT resulted in an increase (P < .05) in the concentration of stimulated cells positive for TNF-alpha and IL-1alpha, however, did not affect the amount of cytokine produced by stimulated monocytes. These results demonstrate that exercise decreases the amount of cytokine produced by LPS-stimulated monocytes, possibly due to elevated levels of circulating stress hormones. Heat stress did not, however, augment the suppression in the amount of cytokine produced by circulating monocytes upon stimulation, despite elevated catecholamines.