Verapamil has been shown to be effective in reducing the frequency of episodes of ischemic pain in patients with unstable angina pectoris, and to be more effective than β-adrenoceptor antagonists in such patients. However, in many patients ischemic symptoms persist despite verapamil therapy. In a group of 33 consecutive patients admitted to the Coronary Care Unit with unstable angina pectoris and treated with verapamil and nitroglycerin, we pro-spectively tested the hypothesis that plasma concentrations of verapamil were a direct determinant of resolution of ischemic symptoms over the initial 72-h period of admission. During this period, improvement or resolution of symptoms occurred in 23 of the 33 patients. With patients receiving 240 to 320 mg/day of verapamil, plasma verapamil concentrations varied between 8 and 487 ng/ml, rising significantly with increasing duration of therapy. Mean plasma verapamil concentrations were somewhat greater in patients who improved than in those with ongoing or worsening symptoms, but the differences were not statistically significant. Furthermore, no correlation was found between symptomatic status and plasma concentrations of norverapamil, the active metabolite of verapamil. In one patient cardiac failure worsened, possibly attributable to an elevated plasma verapamil concentration (336 ng/ml). We conclude that in this clinical setting there is little place for routine monitoring of plasma verapamil concentrations.