A double-blind, crossover study was designed to compare the safety and efficacy of mexiletine with that of placebo in reducing premature ventricular complexes (PVC) in ambulatory patients and to find out the dose which gives a good therapeutic response with a minimal incidence of side-effects. Twenty-six patients, who had on average 427.9 PVCs/hour, were admitted to the study. The doses given were designed to reduce the frequency of PVCs by 50% or more from the baseline value. Two out of the twenty-six patients stopped treatment because of major side-effects. In the remaining twenty-four patients the 3 weeks of treatment with mexiletine significantly reduced the rate of PVCs by comparison with placebo (-63.8% versus +7.5%). In the nineteen responders (per cent reduction of PVCs over 50%) the dose of mexiletine was 600 mg daily (200 mg every 8 hours). In the non-responders plasma levels of mexiletine proved to be in the therapeutic range, not in any way different from responders. The most frequent side-effects were digestive difficulties (fifteen patients taking mexiletine and six taking placebo). These results show that mexiletine is an effective anti-arrhythmic drug in the management of ventricular arrhythmias occurring in ambulatory patients. In the majority of patients mexiletine was found to be effective even at the lowest dose studied of 600 mg/day.