The present study was undertaken to examine the effect of prolonged running on monocyte intracellular cytokine production and plasma cytokine concentration. Blood samples were collected 1 h before, immediately after, 2 h after, and 24 h after a competitive marathon run. There was no change in the number of cells spontaneously producing tumor necrosis factor (TNF)-alpha; however, there was a decrease in the number of cells producing interleukin (IL)-1alpha and IL-6 (P < 0.01) postexercise. In contrast, there was an increase in the number of monocytes that responded to lipopolysaccharide stimulation by producing IL-1alpha, TNF-alpha, and IL-6 (P < 0.01) immediately and 2 h postexercise; however, these cells contained less cytokine (P < 0.05). Plasma IL-6, TNF-alpha, epinephrine, norepinephrine, and cortisol concentrations were markedly increased (P < 0.01) postexercise. These data demonstrate that circulating monocytes are not the source of elevated levels of plasma IL-6 and TNF-alpha after prolonged running. In addition, it is likely that stress hormones result in a decrease in the amount of cytokine produced by LPS-stimulated cells postexercise.