In the patient with Prinzmetal's variant angina, the response to therapy with calcium antagonists may be assessed symptomatically, electrocardiographically (that is, by ambulatory electrocardiographic monitoring), or by response to ergonovine provocation. Although some studies have suggested a good relation between anginal frequency and ergonovine responsiveness in these patients, none has compared ambulatory electrocardiographic activity with the results of ergonovine provocation during the long-term administration of calcium antagonists. Therefore, the present study was performed to compare ergonovine responsiveness with both clinical and ambulatory electrocardiographic activity in patients with Prinzmetal's variant angina during long-term therapy with placebo, verapamil, and nifedipine. Accordingly, 27 patients with variant angina (19 men and 8 women, mean age 52 years) received placebo and verapamil for 2 months each, after which 23 of the 27 also received nifedipine for 2 months. All patients kept a diary of chest pains, and all had weekly 24-hour 2-channel ambulatory electrocardiographic (Holter) monitoring, from which episodes of transient S-T segment deviation were quantitated. During the final week of therapy with each agent, ergonovine was administered, beginning at 0.025 mg and incrementally increasing to 0.20 mg. It was discontinued when the patient had chest pain with S-T segment elevation greater than or equal to 0.1 mV or received a total dose of 0.50 mg. Of the 74 tests, 59 were negative; 6 of the negative tests occurred during a treatment period in which the patient had greater than 10 chest pains/week and greater than 25 episodes of S-T segment deviation/week. Of the 15 positive tests, 8 became positive during administration of less than 0.20 mg ergonovine; 5 of the positive tests occurred during a treatment period in which the patient had no chest pain or S-T segment deviation. Thus, in patients with variant angina, disease activity cannot be monitored reliably by ergonovine provocation because some patients have negative ergonovine tests at a time of marked clinical and electrocardiographic activity, whereas others have positive tests at a time of little (or no) disease activity.