Stimulated by increasing evidence of an inverse relationship between plasma high-density lipoprotein cholesterol level and frequency of coronary heart disease, we determined concentrations of fasting plasma cholesterol, triglyceride, and lipoproteins in 41 very active men (running greater than 15 miles/wk for the previous year) 35-59 years of age (mean age, 47) and in a comparison group of men of similar age, randomly selected from three northern California communities. The runners had significantly (p less than 0.05) decreased mean plasma triglyceride (70 versus 146 mg/100 ml), total plasma cholesterol (200 versus 210 mg/100 ml), and low-density lipoprotein (LDL) cholesterol (125 versus 139 mg/100 ml) concentrations, and a higher mean level of high-density lipoprotein (HDL) cholesterol (64 versus 43 mg/100 ml) than the comparison group (n equals 147 for HDL and LDL; n equals 743 for total cholesterol and triglycerides). These very active men exhibited a plasma lipoprotein profile resembling that of younger women rather tan of sedentary, middle-aged men. This characteristic, and apparently advantageous, pattern could be only partially accounted for by differences in adiposity between runners and control subjects.