A low plasma homocyst(e)ine concentration in premenopausal and pregnant women compared with postmenopausal women and men suggests that steroid hormones are nongenetic factors affecting homocysteine metabolism. This hypothesis was tested by determining plasma homocyst(e)ine levels in adult male rats treated with cortisol, estradiol, or a combination of both. Mean plasma homocyst(e)ine concentrations were 3.71 +/- 0.71, 5.26 +/- 1.76, and 4.28 +/- 0.84 nmol/mL in cortisol-treated, estradiol-treated, and cortisol plus estradiol-treated groups, respectively. These values were substantially low compared with the level of 7.32 +/- 0.89 nmol/mL plasma homocyst(e)ine in the control group, indicating a significant effect of steroid hormones on homocysteine metabolism.