After age 40 years, coronary artery disease (CAD) is the leading cause of death in both women and men, yet in women the factors associated with, or leading to, CAD have been less extensively studied. This study examined the strength of association of a number of risk factors to CAD in groups of women < 60 years of age with (n = 108) and without (n = 66) angiographically documented significant narrowing of coronary arteries. In univariate analyses, there were significant differences between control subjects and patients with regard to age (49 +/- 6 vs 52 +/- 7 years) and total lipids and apolipoproteins measured. The relative frequency of cigarette smoking and diabetes was higher and that of estrogen replacement therapy lower in patients with CAD than in control subjects. In multivariate analysis the following factors were independently associated with CAD (adjusted odds ratios and 95% confidence intervals): total cholesterol to high-density lipoprotein (HDL) cholesterol (1.91; 1.56 to 2.34); lipoprotein (a) (10.66; 3.51 to 32.35); estrogen replacement (0.24; 0.11 to 0.54); age (1.12; 1.04 to 1.18); and smoking (1.50; 0.98 to 2.29). The nonadjusted odds ratio of CAD, based on combined tercile values of lipoprotein (a) serum level and total cholesterol to HDL cholesterol ratio, was very low (0.15; 0.06 to 0.36) when both values were within the first tercile, but very high (16.63; 3.54 to 78.07) when both were in the third tercile.(ABSTRACT TRUNCATED AT 250 WORDS)