The effects of class I, II, III and IV antiarrhythmic drugs (as classified by Vaughan Williams 1974), tetrodotoxin and beta 2-adrenoceptor antagonists on the extraneuronal accumulation of isoprenaline were examined in isolated rat hearts perfused with 3H-isoprenaline (1 mumol/l) and tropolone (100 mumol/l) for 30 min at a constant flow rate (6.5 ml/min) at 40 degrees C. Quinidine (class I), verapamil (IV), diltiazem (IV), dilazep (IV), nifedipine (IV), tetrodotoxin and butoxamine, at a concentration of 10 mumol/l, significantly decreased the extraneuronal accumulation of isoprenaline. The present study demonstrated that quinidine (class I) and all of the calcium channel blockers (class IV) had potent inhibitory effects on the extraneuronal accumulation of isoprenaline. The concentrations of these drugs needed for this decrease were nearly comparable to those needed to suppress isoprenaline-tropolone-induced ventricular fibrillation (Sono et al. 1985a). The antiarrhythmic effects of quinidine and calcium channel blockers in this experimental model may be partly due to a decrease in the extraneuronal accumulation of isoprenaline.