Study was undertaken to assess whether proarrhythmic response to antiarrhythmic drug is a risk factor for cardiac death in patients (pts) with ischaemic heart disease (IHD). In 782 pts with IHD and frequent and/or complex ventricular ectopic beats (VEB) 1041 drug tests guided by 24 hour Holter monitoring were conducted. The following drugs were assessed: propranolol, disopyramide, mexiletine, amiodarone. Pro-arrhythmia was defined according to Velebit: 1/greater than or equal to 4-fold increase in VEBs, 2/greater than or equal to 10-fold increase in repetitive forms of 3/new occurrence of ventricular tachycardia or ventricular fibrillation (VT/VF). Proarrhythmic effect was observed in 8.4% of pts and in 7.9% of drug tests. The frequency with individual drugs ranged from 5.7% to 9%. No drug was completely free of this type of reaction. Antiarrhythmic drugs inducing arrhythmogenic response were eliminated. Pts were followed-up for a mean of 22 months (range 1-49). Chronic antiarrhythmic treatment was conducted. Pts were discharged taking the agent deemed most effective for suppression of arrhythmia. Follow-up visits were made every 6-12 months. All cases of death were verified. In long-term observation cardiac death and sudden death occurred in 53 and 32 pts. With actuarial analysis (Kaplan-Meler method, log rank test) there was significant difference in cardiac death (p less than 0.05) of pro-arrhythmia (+) compared with ++pro-arrhythmia (-) pts at yr (11% v 4%, 7% v 3%) and 3 yr (24% x 11%, 16% v 7%). The relative importance of baseline clinical variables in predicting survival was assessed with a stepwise Cox regression.(ABSTRACT TRUNCATED AT 250 WORDS)