There are conflicting results concerning the anti-ischemic effect of nifedipine in patients with chronic stable angina. Therefore, the purpose of this study was to assess whether the anti-ischemic effect of nifedipine may be related to coronary collateral circulation. Forty-one patients with stable angina and coronary artery disease were randomized to a parallel double-blind study with nifedipine and metoprolol, and compared for effects on transient ischemic episodes during ambulatory electrocardiographic monitoring and exercise-induced ischemia. The effects were correlated to the presence of collateral circulation. In 17 patients, angiographically poor or no collateral flow was observed (group 1), and 24 had good collateral flow (group 2). Nifedipine was administered to 20 patients (8 in group 1, and 12 in group 2). In group 1, nifedipine reduced the frequency of total and asymptomatic ischemic episodes (p < 0.05), whereas significant increases in both total (p < 0.05) and silent (p < 0.01) ischemia were observed in group 2. Exercise variables were slightly improved (p = NS) during nifedipine therapy in group 1, and slightly worsened (p = NS) in group 2. Reflex tachycardia was not observed at either the onset of transient ischemia out of the hospital or exercise-induced ischemia. This was in contrast with the effect in 21 patients treated with metoprolol (9 in group 1, and 12 in group 2) where significant reductions were observed in the frequency of both total (p < 0.01) and silent (p < 0.01) ischemia in both groups. Furthermore, a beneficial effect was observed on all exercise variables.(ABSTRACT TRUNCATED AT 250 WORDS)