Intraseptal administration of heart conditioned medium (HCM) stimulates the growth of injured cholinergic fibers into iris implants placed in the anterodorsal hippocampus. The aims of the present report were to monitor muscarinic cholinergic receptor concentrations during denervation and central innervation of the peripheral tissue targets, and to evaluate the effect of HCM on these changes. For 0, 4, 8, 16 and 28 days after mechanical injury to septohippocampal axons, animals received either intraseptal injections of HCM or control vehicle. Binding of [3H]quinuclidinylbenzilate ([3H]QNB) within iris implants was used as an index of cholinergic muscarinic receptor concentration. The results indicate that within the iris implants: (1) a dramatic drop in the number of muscarinic receptors is observed 4 days after denervation; (2) under control conditions, central cholinergic innervation is not associated with muscarinic receptor recovery; and (3) after administration of HCM, muscarinic receptor levels begin to increase within two weeks and approach the pre-lesion endogenous concentration following 28 days of treatment. These results support the hypothesis that trophic factors may facilitate the restoration of effective, appropriate connections between nerve fibers and their targets.