Women with polycystic ovary syndrome (PCOS) have a clustering of cardiovascular risk factors, such as obesity, lipid abnormalities, impaired glucose tolerance, insulin resistance, and hypertension. Exercise is reported to lower the incidence of cardiac events. The effect of exercise on plasma homocysteine concentrations, an independent cardiovascular risk factor, has not been previously reported in women with PCOS. We examined the effects of exercise on plasma total homocysteine concentrations in young overweight or obese PCOS women [age (mean +/- SD), 30.6 +/- 6.6 yr; body mass index, 35.49 +/- 7.57 kg/m(2)]. Twenty-one women consented to a 6-month exercise program; 12 women (exercisers) adhered to the program, whereas 9 (nonexercisers) did not. In both groups of women, the following parameters were recorded at baseline and 6 months: body mass index, waist-to-hip ratio, and aerobic capacity (maximal oxygen consumption); blood samples were taken after an overnight fast for plasma total homocysteine, insulin, and other biochemical parameters. A significant decrease in plasma total homocysteine concentrations (P < 0.001) and waist-to-hip ratio (P = 0.041) and a significant increase in maximal oxygen consumption (P = 0.019) were recorded at 6 months, compared with baseline in the exercise group. This decrease in homocysteine was not explained by changes in anthropometric or biochemical parameters. In contrast, no significant changes in any of the variables were observed in the nonexercise group. Our study has provided the first evidence that regular exercise significantly lowers plasma homocysteine in young overweight or obese women with PCOS, a group at increased risk of premature atherosclerosis. The precise mechanism by which exercise is associated with a reduction in homocysteine remains to be elucidated.