In the rabbit, vagotomy combined with arterial baroreceptor denervation abolishes the renal sympathoinhibition elicited by volume expansion. However, the effect of removing cardiopulmonary afferents alone has not been investigated. The aim of the present study was to determine the role of the cardiac afferents in the renal sympathetic response elicited by volume expansion in the normal conscious rabbit. Four experimental groups were used in which rabbits were administered 1) volume expansion (Haemaccel, 1.9 ml/min for 60 min), 2) volume expansion + bolus intrapericardial procaine (20 mg) to block cardiac afferents, 3) volume expansion + intravenous procaine (20 mg bolus), and 4) intrapericardial procaine alone (20 mg bolus). Volume expansion did not significantly affect mean arterial pressure or heart rate but produced a profound fall in renal sympathetic nerve activity (approximately 50%). Intrapericardial procaine administered 30 min after the start of volume expansion markedly reversed the renal sympathoinhibition to within 20% of the pre-volume expansion level, an effect that wore off over 25 min. In contrast, intravenous procaine lowered renal sympathetic nerve activity slightly further. The results suggest that cardiac afferents play the dominant role in the renal sympathoinhibition in response to volume expansion in the normal conscious rabbit.