An extreme form of hyperalphalipoproteinemia was studied in a patient affected by multiple symmetric lipomatosis (MSL); four relatives and three MSL controls were also evaluated. Plasma lipids and apolipoproteins were measured and overall lipoprotein profile was assessed by density gradient ultracentrifugation. The patient showed a plasma HDL-cholesterol of 138 mg/dl and an apo A-I of 218 mg/dl; moreover significantly high HDL levels were found in two unaffected relatives. The hypobetalipoproteinemia trait was also found both in the patient and in one of his daughters. We suggest that some pre-existing conditions may enhance lipoprotein metabolism alterations in this lipid storage disease.