Long-term treatment of breast-cancer patients with the anti-oestrogen tamoxifen has been found to be associated with reduced cardiovascular mortality. Plasma homocysteine is an independent risk factor for atherosclerotic disease, and its level is determined by folate and cobalamin status, and possibly also by oestrogen status. We measured the effect of tamoxifen on plasma homocysteine, serum cholesterol, serum cobalamin and serum and erythrocyte folate in 31 post-menopausal women with breast cancer. The plasma homocysteine level was decreased by a mean value of 29.8% after 9–12 months and by 24.5% after 13–18 months of treatment. Tamoxifen suppressed serum cholesterol by mean values varying between 7.2% and 17.6% after 3 to 19 months of treatment. There was no correlation between changes in plasma homocysteine and serum cholesterol. These findings suggest that the homocysteine-lowering effect of tamoxifen may contribute to the reduction of cardiovascular mortality observed in patients on adjuvant therapy with tamoxifen. © 1995 Wiley-Liss, Inc.