More than 20 studies have been conducted to assess the effects of estrogen replacement on coronary heart disease. The majority of these studies have demonstrated a protective effect of the use of estrogen replacement therapy. Most of these studies have been limited to the postmenopausal use of estrogen alone. Data on the combined use of estrogen and progestin, currently recommended for women who have not undergone a hysterectomy, are more limited. This report assesses the associations of therapy with exogenous estrogen alone, or estrogen combined with progestin, with physical variables related to cardiovascular risk in a large sample of postmenopausal women. This cross-sectional analysis used data from the Athero-sclerosis Risk in Communities study. The study cohort comprised four population-based samples from Forsyth County, NC, Jackson, MS, selected suburbs of Minneapolis, and Washington County, MD. To examine the associations of hormone-replacement therapy, 4958 postmenopausal women participating in this population-based investigation were studied. Women were classified into four groups according to their use of hormone-replacement therapy: current users of estrogen alone, current users of estrogen with progestin, nonusers who had formerly used these hormones, and nonusers who had never used them. Concentrations of plasma lipids, hemostatic factors, fasting serum concentrations of glucose, insulin, and blood pressure were measured. Current users had higher levels of high-density lipoprotein cholesterol and its subfraction than did nonusers, and lower mean levels of low-density lipoprotein cholesterol, apolipo-protein B, fibrinogen, antithrombin III, and fasting serum glucose, and insulin (Table 1). Current users of estrogen alone had higher triglyceride, factor A, and protein C levels than other nonusers or current users of estrogen with progesterone. After making certain assumptions, the authors estimate that if the findings are causal, women using hormone-replacement therapy would have a 42 per cent decrease in the risk of coronary heart disease. Women using estrogen with progestin would have an even greater estimated benefit.