Tertatolol is a noncardioselective beta-blocker without intrinsic sympathomimetic activity. In a preliminary 3-month open study, it was shown that T was devoid of any atherogenic effect since HDL-cholesterol (HDL-C) and apoprotein levels did not change for 3 months of therapy. To investigate the long-term effects of tertatolol on the lipid profile and its safety in hypertensive patients with peripheral arterial disease (PAD), a 9-month, randomized, double-blind, parallel group study was carried out in 40 patients. Tertatolol 5 mg once daily was compared with metoprolol 200 mg once daily. If BP was not controlled after 2 months, a vasodilatator agent, dihydralazine, was added at the lowest dose required to control BP (diastolic BP < 90 mm Hg). Lipoprotein fractions and apoproteins were assayed before (MO) and after 2, 6 and 9 months of therapy. At the same occasions, peripheral arterial disease (PAD) was evaluated on exercise tests carried out on a treadmill and on the regional blood flow measured in the ankle arteries by the Doppler technique. Four patients were not eligible for analysis. In the tertatolol group, 1 patient with a normal BP, and 2 patients who dropped out, 1 because of persistent nausea and 1 because of personal reasons. In the metoprolol group, 1 patient refused to take dihydralazine. In the 35 fully documented patients, BP control was achieved in both groups. The mean reductions in supine systolic/diastolic BP were 31.4/14.6 and 34.7/17.1 mm Hg in the tertatolol and metoprolol groups, respectively. Throughout the 9 months, no significant difference between groups was observed in the change of lipid parameters, except for the apoprotein A2 level which increased significantly with tertatolol (+24 vs. +3% with metoprolol, p = 0.043). Changes in lipid profile were less marked with tertatolol than with metoprolol: triglycerides increased by 2 and by 13% with tertatolol and metoprolol, respectively. HDL-cholesterol decreased by 11 % with metoprolol and increased by 2% with tertatolol. Total and LDL·cholesterol remained stable with both drugs. The apo Al/apo B ratio, which inversely correlates with the atherogenic risk, decreased by 7 and 25% with tertatolol and metoprolol, respectively. Peripheral arterial disease improved with both drugs: pain-free walking distance increased by 33.0 and 51.6 m with metoprolol and tertatolol, respectively. Residual pressure index remained unchanged with both drugs since the calf BP measured in the ankle arteries decreased in proportion to the decrease in brachial BP. Thus, both drugs were effective and well-tolerated since they controlled BP and improved the intermittent claudication. Considering its beneficial effects on the lipid parameters, tertatolol could be a better choice than metoprolol in the treatment of hypertensive patients with severe PAD.