We studied the long-term effects of membrane-active antiarrhythmic agents on chronic ventricular arrhythmias in patients who have survived prehospital cardiac arrest. Among 16 patients treated with a dose-adjusted, plasma level-monitored antiarrhythmic regimen, eight have survived for longer than 12 months eight have had recurrent cardiac arrests (RCAs). Monthly Holter monitor tapes (HIM) recorded during the 4 months before the eight RCAs were compared with monthly HM tapes matched for time of entry duration of follow-up in the eight patients who did not have RCAs. Transient or persistent complex ventricular ectopic depolarizations (VEDs) have been recorded on 47 of the 63 monthly HM tapes (75%). The difference between VEDs in the RCA patients (mean 153 VEDs/hr, median 19 VEDs/hr) VEDs in the patients who have not had RCA (mean 122 VEDs/hr, median 8 VEDs/hr) was not significant (p ≥ 0.2); nor was there a predictable relationship between therapeutic plasma levels of antiarrhythmic agents the frequency complexity of chronic asymptomatic VEDs (therapeutic levels mean 104 VEDs/hr, median 6 VEDs/hr; subtherapeutic levels – mean 184 VEDs/hr, median 21 VEDs/hr). Differences were not significant (p ≥ 0.1). In contrast, all eight RCA patients had unstable plasma levels (21 of 31 determinations subtherapeutic) while six of the eight patients who have not had RCA had consistently therapeutic levels (p ≤ 0.01). Thus, adequate plasma levels of antiarrhythmic agents may protect against RCA, despite failure to suppress VEDs predictably. The apparent dissociation between predictable suppression of chronic VEDs protection against RCA suggests that clinical effectiveness of these agents may not be best measured by their effect on chronic VEDs.