The effects of atenolol (100 mg/day) and nifedipine (20 mg 3 times daily) and their combination on ambulant myocardial ischemia were investigated using a randomized, double-blind, placebo-controlled, crossover trial. Eighteen men with symptomatic coronary artery disease, exercise-induced ischemia and minimal symptoms, underwent 4 blinded treatment periods of 2 weeks' duration (2 placebo, 1 atenolol, 1 nifedipine). Those that did not have ischemia eliminated by monotherapy received combination therapy with both drugs. Forty-eight-hour ambulatory electrocardiographic monitoring was used to quantitate ischemic parameters at the end of each period. Both nifedipine and atenolol as monotherapy reduced the number of ischemic episodes and the average duration of each episode compared with placebo (p less than 0.05). Compared with placebo, nifedipine reduced the total duration of ischemia (p less than 0.05) but the effect of atenolol on ischemia duration was of borderline significance (p = 0.066). There were no differences in reduction of ischemic parameters when atenolol was compared with nifedipine (difference not significant). In the 9 patients who continued to have ischemia with monotherapy, combination therapy eliminated it in 2 and reduced the duration by greater than 50% in the remaining patients compared with placebo. In conclusion, monotherapy with nifedipine or atenolol is similarly effective in eliminating or reducing ambulant ischemia. Combination therapy can provide additional benefit in those with continued ischemia.