The intrinsic cardiac nerves (ICN) have been shown to develop supersensitivity to nicotine (NIC) following complete extrinsic cardiac denervation. The present experiments were performed to delineate the pattern of ICN distribution in the heart by examining the pattern of NIC supersensitivity after unilateral vagotomy (VGX). Thirty-eight dogs were placed on cardiopulmonary bypass and inotropy evaluated by means of isovolumic pressures from fluid-filled balloons placed in the atria and ventricles. The animals were divided into three groups: group I, sham-operated controls; group II, animals studied 1-2 wk after VGX; and group III, animals studied 8-12 wk after VGX. Chronotropic and inotropic responses were evaluated in terms of NIC and acetylcholine (ACh) dose-response curves as well as frequency-response curves to stimulation of the intact vagus nerve (0.5-30 Hz). No change in NIC sensitivity was observed in group II, and vagal frequency-response curves were identical to group I. In group III dogs, both the right atrium and right ventricle showed significant increases in NIC sensitivity after left vagotomy. All group III animals showed right-shifted frequency-response curves. We conclude that nicotinic supersensitivity of the ICN and inotropic unresponsiveness to vagal stimulation occur but are slow in developing (70-130 days); and preganglionic sprouting does not appear to play a functional role in the adjustment of cardiac control mechanisms to unilateral vagotomy.