Cardiac reactivity has been determined in rats with acute renal failure (ARF) induced by either bilateral nephrectomy or intramuscular glycerol injection. Rats with bilateral nephrectomy showed reduced chronotropic responses to cervical sympathetic stimulation but no appreciable alteration in the chronotropic responses to vagal stimulation. By contrast, we have previously noted that rats with glycerol-induced ARF show diminished chronotropic responses to stimulation of both nerves. The negative chronotropic and inotropic responses to carbachol in isolated atria from both nephrectomized and glycerol-injected rats were not significantly different from their respective controls. In both models of ARF the atrial positive chronotropic responses to isoprenaline were significantly decreased whilst positive inotropic responses were not significantly different from controls. The results indicate that the cause of the reduced chronotropic response to vagal stimulation observed in glycerol-injected rats is of presynaptic origin whilst the reduced chronotropic response to cervical sympathetic stimulation noted in both models of ARF may be due to an impaired postsynaptic response.