We investigated whether regular aerobic exercise could affect plasma total homocysteine (tHcy), and whether there were sex-related or racial differences in tHcy changes. Data were available for 816 black and white men and women, aged 17-65 years, 711 of whom completed a 20 week aerobic exercise training program. The tHcy concentration was measured in frozen plasma samples by an HPLC method. In Blacks, tHcy did not change with exercise training [men -0.5 (SD 3.7) micromol/l, women 0.0 (2.2) micromol/l) but increased significantly in Whites (men +0.3 (1.7) micromol/l, women +0.2 (1.6) micromol/l). No sex-related differences were found in either racial group. Changes in tHcy correlated negatively with baseline homocysteine (r = -0.40, P < 0.0001). Homocysteine levels of the "High" (hyperhomocysteinemia) (>or=15 micromol/l) group (n = 30) decreased significantly with regular aerobic exercise from 23.1 (12.1) to 19.6 (7.6) micromol/l. Homocysteine levels of the "Normal" group increased slightly from 8.2 +/- 2.2 to 8.5 +/- 2.4 micromol/l. Men exhibit racial differences for tHcy responses to exercise training. Regular aerobic exercise has favorable effects on individuals with hyperhomocysteinemia, but tHcy slightly increased in individuals within the normal range.