Changes in heart rate were monitored in response to supramaximal electrical stimulation of the spinal sympathetic cardiac nerves in the pithed rat. 2. Submaximal positive chronotropic responses of the heart to stimulation (0.1-1.0 Hz) were inhibited after intravenous injection of the alpha 2-adrenoreceptor agonists B-HT 920 and xylazine, but not after the alpha 1-adrenoreceptor agonist methoxamine. 3. The alpha 2-adrenoreceptor antagonist yohimbine or idazoxan but not the alpha 1-adrenoreceptor antagonist prazosin, given intravenously, reduced the inhibitory effect of B-HT 920 on positive chronotropic responses to cardiac sympathetic nerve stimulation. Neither yohimbine, idazoxan nor prazosin had any effect on positive chronotropic responses to nerve stimulation. 4. Desmethylimipramine (DMI) potentiated the increased heart rate during continuous stimulation of the cardiac nerves at 0.2 Hz. Responses to stimulation, at this frequency, were unaffected by yohimbine, either in the absence or presence of the neuronal uptake inhibitor, DMI. 5. Intravenous infusion of the angiotensin antagonist saralasin or injection of the angiotensin converting enzyme inhibitor captopril had no significant effect, either on positive chronotropic responses to stimulation or on the inhibitory effects of B-HT 920. Positive chronotropic responses to stimulation were also unaffected by yohimbine in the presence of captopril, indomethacin, or indomethacin plus captopril. 6. Although presynaptic effects of alpha 2-agonists and their antagonists on cardiac nerve function were demonstrated, no evidence was obtained that prejunctional alpha 2-adrenoreceptors modulate transmission during continuous supramaximal firing at constant frequency.(ABSTRACT TRUNCATED AT 250 WORDS)