The relationship between the accumulation of isoprenaline and the incidence and duration of ventricular fibrillation was investigated in the perfused rat heart. Isolated rat hearts were perfused with 3H-isoprenaline (1 mumol/l) for 30 min at a constant flow rate of 6.5 ml/min at a temperature between 40 and 41 degrees C. Electrocardiograms were recorded during the perfusion period and the isoprenaline content of the tissue was measured after the perfusion. The accumulation of isoprenaline was significantly increased and the duration of ventricular fibrillation was significantly prolonged by the presence of tropolone (100 mumol/l). When extraneuronal uptake inhibitors such as normetanephrine (100 mumol/l), 3-O-methylisoprenaline (100 mumol/l) or phenoxybenzamine (1 mumol/l) were added to the perfusion fluid containing 3H-isoprenaline (1 mumol/l) and tropolone (100 mumol/l), the accumulation of isoprenaline was significantly decreased, the incidence of ventricular fibrillation was significantly reduced and the duration of ventricular fibrillation was significantly shortened. There was a significant correlation for dependence of duration of ventricular fibrillation on the isoprenaline content of rat hearts perfused with various extraneuronal uptake inhibitors in the presence of tropolone (correlation coefficient [r] = 0.62, P less than 0.001). These results indicate that the accumulation of isoprenaline in perfused rat hearts relates to the occurrence and duration of ventricular fibrillation.