To examine the effect of zinc (Zn) supplementation on exercise-induced changes in immune function, five male runners were randomly assigned in a double-blind crossover design to take a supplement (S; 25 mg of Zn and 1.5 mg of copper) or placebo (P) twice daily for 6 days. On morning 4 of each phase, 1 h after taking S or P, subjects ran on a treadmill at 70-75% of maximal oxygen uptake until exhaustion (similar to 2 h). Blood samples were obtained before (Pre), immediately after (Post), and 1 (Recl) and 2 (Rec2) days after the run. [H-3]thymidine incorporation by mitogen-treated mononuclear cell cultures was significantly lower (P < 0.05) Post than Pre, Recl, or Rec2 for both S and P. Respiratory burst activity of isolated neutrophils was enhanced after exercise with P but not with S (P: Pre 12.0 +/- 1.1 vs. Post 17.6 +/- 2.3 nmol O-2(-)/10(6) cells; S: Pre 11.7 +/- 0.3 vs. Post 12.1 +/- 1.2 nmol O-2(-)/10(6) cells). Thus supplemental Zn blocked the exercise-induced increase in reactive oxygen species. Whether this antioxidant effect of Zn will benefit individuals exposed to chronic physical stress remains to be determined.