The responses of 14 hyperlipidemic subjects to 4 hypolipidemic agents were compared by measuring cholesterol and triglyceride in whole plasma, very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL) monthly for 2 months before and 3 months during treatment with each of 4 drugs: clofibrate, 2 g/d; colestipol, 20 g/d; para-aminosalicylic acid-ascorbate (PAS-C), 6-8 g/d; and oxandrolone, 7.5 mg/d. Lipid responses proved to be stable by the first monthly evaluation both off and on each drug. Mean adherence was high and similar for all agents (81-92% of the prescribed dose). Clofibrate was associated with significant decreases in mean plasma cholesterol (-16%, p less than .01), plasma triglyceride (-51%, p less than .005), VLDL-cholesterol (-61%, p less than .005) and VLDL-triglyceride (-61%, P less than .005), while HDL cholesterol increased (+20%, p less than .01), and the LDL-cholesterol/HDL ratio declined (-24%, p less than .05). Colestipol was associated with decreases in mean plasma cholesterol (-15%, p less than .01) and LDL-cholesterol (-22%, p less than .05), while VLDL-triglyceride increased (+41%, p less than .05), and the LDL-cholesterol/HDL-cholesterol radio declined (-25%, p less than .05). PAS-C was associated with decreases in VLDL-cholesterol (-30%, p less than .05), and VLDL-triglyceride (-29%, p less than .05), while the LDL-cholesterol/HDL-cholesterol ratio remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)