The effects of hypoxia, adrenaline perfusion, and their combination on cardiac rhythm were studied in the isolated perfused heart of the guinea-pig. 2. Hypoxia or adrenaline perfusion (5.5 mumol/l) produced a low incidence of ventricular arrhythmias (26% and 33%, respectively); however, the changes were not statistically significant. 3. A combination of hypoxia and adrenaline perfusion produced ventricular arrhythmias in each of twenty-three preparations: there were frequent ventricular premature contractions in eighteen preparations, and ventricular tachycardia or fibrillation in five preparations. The mean times of onset of these arrhythmias after hypoxia were 33.3 min (s.e.m. = 5.2) and 57.6 min (s.e.m. = 4.7), respectively. 4. The responsiveness of the frequent ventricular premature contractions to the antiarrhythmic effects of quinidine and lignocaine was tested in twelve preparations. Both drugs produced dose-dependent reductions in the percentage of ventricular ectopic beats. 5. These results suggest that a combination of hypoxia and adrenaline perfusion is a simple but reliable method of inducing ventricular arrhythmias in the isolated heart of the guinea-pig, and this provides a model that may be useful for the experimental evaluation of antiarrhythmic drugs.