We report on serum lipoprotein changes after antihypertensive therapy in nine subjects with type II hyperlipoproteinemia and eight subjects with normolipidemia. They received placebo for 6 wk, followed by random order crossover between methyldopa and propranolol for 6 mo. Physical activity, diet, and other drugs were monitored for constancy. No other antihypertensive drugs were used. Doses required for normalization of blood pressure ranged between 40 to 360 mg/day for propranolol and 500 to 2500 mg/day for methyldopa. Mean blood pressure was equally lowered to normal by both drugs. Triglyceride levels increased after propranolol and after methyldopa. Subjects with normocholesterolemia developed higher serum triglyceride levels after each drug, whereas such a change did not occur in patients with hypercholesterolemia. Low-density lipoprotein cholesterol levels were reduced by methyldopa only in patients with baseline hypercholesterolemia. There was no correlation between lipoprotein level changes, dose required of either drug, or propranolol blood levels. The baseline lipoprotein metabolism disorder appears more likely to determine the type of changes in serum lipoprotein levels after these antihypertensive drugs.