In order to evaluate long-term efficacy of a new calcium antagonist, diltiazem, for therapy of coronary artery spasm, 16 patients with clinical variant angina due to documented coronary artery spasm participated in a 44-week prospective, randomized, double-blind cross-over trial of 240 mg of diltiazem vs. placebo. The study involved eleven 28-day cycles of which one of the first five cycles (phase 1) and one of the last six cycles (phase 2) were placebo, with the remainder being active medication. Response was assessed with the dairy technique, measuring frequency of angina and side effects. When diltiazem was compared with the placebo period during phase 1, there was a 73% decrease in frequency of angina from 1.1 to 0.3 episodes per day (P less than 0.01). When diltiazem was compared with the placebo during phase 2, there was an 80% decrease in frequency of angina from 0.5 to 0.1 episodes per day (P less than 0.05). When phase 1 placebo cycle was compared with phase 2 placebo cycle, there was a 55% decrease in frequency of angina which approached statistical significance (P less than 0.10). This marked disease attenuation demonstrated during the 44-week study reflects the variability of symptoms of variant angina and possibly reflects a carry-over therapeutic effect of the calcium entry blocker. Adverse side effects were absent in our small group of patients. Diltiazem is effective for the long-term control of symptoms of active coronary artery spasm.