This study examined the effects of a two-month antioxidant vitamin treatment on acute hematological and hemorheological alterations induced by exhausting exercise; both sedentary and trained individuals were employed. Eighteen young male, human subjects (9 sedentary, 9 trained by regular exercise) participated in the study and performed an initial maximal aerobic cycle ergometer exercise with frequent blood sampling over a 24 hour period and analysis of hematological and hemorheological parameters. All subjects were treated with an antioxidant vitamin A, C and E regimen, supplemented orally for two months, then subjected to a second exercise test and blood sampling at the end of this period. In the sedentary group during the first testing period (prior to vitamin treatment), white blood cell counts and granulocyte percentages were increased at 2 hours following the exercise test and remained elevated for 4-12 hours. Red blood cell (RBC) deformability and aggregation were also altered by exercise in the sedentary group prior to vitamin treatment. However, none of these parameters in the sedentary group were altered by exercise following the two month period of antioxidant vitamin treatment. With the exception of a transient rise in granulocyte percentage, these parameters were also not affected in the trained subjects before the vitamin treatment. Significant increases of RBC lipid peroxidation observed 12 hours after the exercise test in both sedentary and trained subjects were also totally prevented by vitamin treatment. Our results indicate that antioxidant vitamin treatment is effective in preventing the inflammation-like response and coincident adverse hemorheological changes following an episode of exhausting exercise, and suggest that such changes may be related to exercise-induced death events.