To assess the relation of lipid levels to angiographic coronary artery disease (CAD), lipid profiles were obtained on 125 men and 72 women undergoing diagnostic coronary angiography. CAD, defined as greater than or equal to 25% diameter narrowing in a major coronary artery, was present in 106 men (85%) and 54 women (75%). Multiple regression analyses revealed that only high-density lipoprotein (HDL) cholesterol level in men, and age and total/HDL cholesterol ratio in women, were independently associated with the presence of CAD after adjustment for other risk factors. HDL cholesterol level and age were significantly correlated with both extent (number of diseased vessels) and severity (percent maximum stenosis) of CAD in men. In women, age was the only independent variable related to severity, whereas age and total/HDL cholesterol ratio were related to extent. Of 71 patients with total cholesterol less than 200 mg/dl, 79% had CAD. With multiple regression analyses, HDL cholesterol was the only variable independently related to the presence and severity of CAD in these patients after adjustment for age and gender; extent was significantly associated with age and male gender, and was unrelated to any of the lipid parameters. With use of multiple logistic and linear regression analyses of the group of 197 patients, HDL cholesterol was the most powerful independent variable associated with the presence and severity of CAD after adjustment for age and gender. HDL cholesterol was also an independent predictor of extent. Age was independently associated with each of the end points examined, and was the variable most significantly related to extent. These data add to the growing body of information demonstrating an important association between HDL and CAD.