This study tested the hypothesis that exercise elicits monocytic cytokine expression and that prolonged cold exposure modulates such responses. Nine men (age, 24.6 +/- 3.8 y; VO(2 peak), 56.8 +/- 5.6 ml. kg(-1). min(-1)) completed 7 days of exhausting exercise (aerobic, anaerobic, resistive) and underwent three cold, wet exposures (CW). CW trials comprised </=6 h (six 1-h rest-work cycles) exposure to cold (5 degrees C, 20 km/h wind) and wet (5 cm/h rain) conditions. Blood samples for the determination of intracellular and serum cytokine levels and circulating hormone concentrations were drawn at rest (0700), after exercise (approximately 1130), and after CW (~2000). Whole blood was incubated with (stimulated) or without (spontaneous) lipopolysaccharide (LPS; 1 microgram/ml) and stained for CD14 monocyte surface antigens. Cell suspensions were stained for intracellular cytokine expression and analyzed by flow cytometry. The proportion of CD14(+) monocytes exhibiting spontaneous and stimulated intracellular expression of interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha increased after exercise, but these cells produced less IL-1beta and TNF-alpha after CW when CW was preceded by exhausting exercise. Serum cytokine concentrations followed a parallel trend. These findings suggest that blood monocytes contribute to exercise-induced cytokinemia and that cold exposure can differentially modulate cytokine production, upregulating expression of IL-6 and IL-1 receptor antagonist but downregulating IL-1beta and TNF-alpha. The cold-induced changes in cytokine expression appear to be linked to enhanced catecholamine secretion associated with cold exposure.