The aim of the study was to compare the effect of slow-release (SR) nicardipine, placebo and chlorthalidone on hypertension-related arrhythmias evaluating 24-h ambulatory ECG. After a 2-week placebo run-in, the patients were randomized according to a double-blind design and treated with either SR nicardipine (40 mg b.i.d.) or chlorthalidone (25 mg once daily) for 8 weeks. At the end of this period, the patients were again treated with placebo for an additional 2 weeks and then crossed over and treated with either SR nicardipine or chlorthalidone for another 8 weeks. Three patients were withdrawn from the study at the end of the first period (1 after SR nicardipine and 2 after chlorthalidone) because of severe arrhythmias (Lown's class 4B) requiring antiarrhythmic therapy. The statistical evaluation was performed on data from 36 patients. SR nicardipine and chlorthalidone determined a significant reduction of both systolic and diastolic BP, with greater decrease with SR nicardipine and without modification of HR. Twenty-four-h ambulatory ECG showed a reduction of both supraventricular and ventricular arrhythmias by SR nicardipine not only compared to placebo but also vs chlorthalidone. Similarly, the severity of ventricular arrhythmias, according to Lown's classes, was reduced only after SR nicardipine. These results were confirmed also dividing the patients according to echocardiographic criteria of LVH. The adverse effects were slight and well tolerated with both drugs. Among hematochemical data, only chlorthalidone induced significant reduction of blood potassium (with 3 cases of hypokalemia). In conclusion, SR nicardipine was found to be more efficacious than chlorthalidone in controlling not only BP but also the arrhythmic events related to hypertension.