Low plasma high density lipoprotein (HDL) cholesterol concentration is a risk factor for coronary heart disease (CHD) and is frequently associated with high triglyceride concentration. Both of these abnormalities have been related to insulin resistance as estimated by plasma insulin concentrations and to measures of obesity, regional adiposity, and physical fitness. To determine which of these variables (fasting plasma insulin, obesity as measured by body mass index [BMI], or regional adiposity as measured by waist to hip ratio [WHR]) best identifies men with low HDL cholesterol and high triglyceride concentrations, we divided 83 men, aged 50-65 years, who were free of CHD or diabetes, into tertiles based on BMI, WHR, or fasting plasma insulin concentration. Only for plasma insulin tertiles were there statistically significant differences in HDL cholesterol (tertile 1, mean +/- SEM, 1.34 +/- 0.08 mmol/l; 2, 1.16 +/- 0.05 mmol/l; 3, 1.10 +/- 0.06 mmol/l; p less than 0.03) and triglyceride (tertile 1, 1.05 +/- 0.08 mmol/l; 2, 1.48 +/- 0.12 mmol/l; 3, 1.82 +/- 0.17 mmol/l; p less than 0.005) concentrations. In forward stepwise regressions with HDL cholesterol and triglyceride as dependent variables, fasting insulin concentration but not BMI, WHR, or maximal oxygen uptake (VO2max), a measure of physical fitness, predicted HDL cholesterol (R2 = 0.07, p less than 0.02) and triglyceride (R2 = 0.20, p less than 0.001) concentrations. The data suggest that plasma insulin concentration is an important predictor of HDL cholesterol and triglyceride concentrations independent of BMI, WHR, or VO2max.