Cholesterol levels in high density lipoprotein subfractions (HDL2 and HDL3) were evaluated in 69 patients (55 males, average age +/- SD 58.3 +/- 8.8, and 14 females, average age +/- SD 63.1 +/- 10.3) with extra-coronary arteriosclerosis (lower limbs, supraaortic trunks and both sites), and in 79 healthy age-matched control subjects. HDL cholesterol was significantly reduced in male and female patients. The HDL cholesterol decrease was due to a fall in both HDL2 and HDL3 cholesterols; nonetheless, an analysis of the HDL2-cholesterol/HDL3-cholesterol ratio disclosed that HDL2 cholesterol was the most reduced. Slightly higher plasma cholesterol and triglyceride levels were found in the patients as well as a higher plasma cholesterol/HDL-cholesterol ratio. On the contrary, the HDL2-cholesterol/HDL3-cholesterol ratio was significantly reduced in the patients. These preliminary findings suggest that, as in ischemic heart disease, the HDL cholesterol reduction in cerebral and peripheral arteriosclerosis is also mainly due to a reduction in the HDL2 subfraction. These results also lend further support to the proposal that determination of the HDL subfractions is useful for a better assessment of the risk profile for arteriosclerosis.