Homocysteinemia is associated with juvenile arteriosclerosis, recurrent thromboembolic complications and osteoporosis. Plasma homocysteine, measured as homocysteine-cysteine mixed disulfide (MDS), has in other than homocysteinemics been reported to be higher in patients with coronary heart or cerebrovascular disease than in controls, and higher in men than in premenopausal women. Here, in groups of normal men and normal premenopausal and postmenopausal women, we measured plasma MDS in the fasting state and four hours after a methionine load (100 mg/kg body weight), before and after four weeks of folic acid therapy at 5 mg daily. In their fasting plasma, postmenopausal women (n = 5) had significantly (P less than 0.05) higher MDS concentrations than premenopausal women (n = 5) and younger men (n = 5). After the methionine load MDS concentrations in postmenopausal women rose markedly, reaching levels significantly higher than those in younger men (P less than 0.05), and with no overlap with values in premenopausal women (P less than 0.01), or in older men (n = 5, P less than 0.01). Folic acid therapy resulted in substantial reductions (n = 15, P less than 0.01) of MDS concentrations both before the methionine load (-31%) and after (-28%), though subjects had initially had normal concentrations of serum and erythrocyte folates. We speculate that moderate homocysteinemia might contribute to postmenopausal arteriosclerosis and osteoporosis. Should this prove to be the case, folic acid might be a useful prophylactic.