To determine whether cigarette smoking affects the results of drug treatment for angina, 10 cigarette smokers with angina were given placebo, nifedipine (60 mg/day), propranolol (240 mg/day) and atenolol (100 mg/day), each for 1 wk. The 4-wk double-blind study was repeated with the same randomly determined order of drug sequences, after all 10 subjects had stopped smoking. Before and after the subjects stopped smoking, all 3 drugs significantly reduced the frequency of angina, as measured with angina diaries, and improved the results of maximal exercise testing and 48-h ambulatory monitoring of ST segments (P < 0.01). During the nonsmoking phase of the study, there was an overall decline in the frequency of angina and an improvement in performance on exercise testing (P < 0.05) as compared with the smoking period, although the results of 48-h ambulatory monitoring remained unchanged. Improvement after patients stopped smoking was greater during treatment with nifedipine than during administration of the other 2 drugs or placebo. Blood levels of propranolol were increased when patients stopped smoking; levels of nifedipine and atenolol were unchanged. Smoking had direct and adverse effects on the heart and interfered with the efficacy of all 3 anti-anginal drugs, but with nifedipine the most.