OBJECTIVE The aim of the study was to investigate the differential effects of the class III agent, d-sotalol, on conduction and refractoriness on normal and infarcted areas of the canine ventricle. METHODS Epicardial mapping studies were performed in 6 dogs 5-7 days after ligation of the left descending coronary artery using a specially designed patch electrode which contained 192 bipolar electrodes. Normal and infarcted areas were differentiated with respect to their macroscopic appearance and electrophysiological properties. Activation maps and local effective refractory periods (ERP) were determined before and after the administration of d-sotalol (1.5 mg/kg) at cycle lengths of 250, 300 and 350 ms. RESULTS Conduction and refractoriness were relatively homogeneous in the normal zone (NZ), contrasting with inhomogeneity in the infarct zone (IZ). In 2 dogs d-sotalol produced regional delay and block of conduction, exclusively in the IZ. The relative increase in refractoriness (delta ERP) after d-sotalol was significantly more pronounced in the IZ than in vs the NZ. In the NZ, delta ERP was most prominent at the longest (350 ms) and least prominent at the shortest (250 ms) basic pacing cycle lengths (11.5 +/- 2.8 vs. 7.3 +/- 1.4%; P < 0.05). The effect of d-sotalol in the IZ was independent of the basic pacing cycle length. CONCLUSIONS d-Sotalol preferentially prolonged refractoriness in the IZ of the canine ventricle. This effect and the lack of rate-dependence in the IZ could provide a possible explanation for both the potent antiarrhythmic and potential antiarrhythmic effect of d-sotalol.