Neurotransmitters are thought to influence cell development in their target tissues. In the current study, neonatal rats were given 6-hydroxydopamine to produce permanent sympathetic denervation, and the effects on cardiac and hepatic DNA and protein synthesis were assessed. Lesioned animals showed deficits in cardiac DNA synthesis over the first 8 d postpartum, a period in which sympathetic innervation is sparse and synaptic norepinephrine concentrations are low; the effect of lesioning was also evident for protein synthesis. Subsequently, DNA synthesis in control animals declined precipitously during the second to third postnatal week, the phase associated with ingrowth of the majority of sympathetic terminals and sympathetic hyperactivity. Neonatal lesioning delayed the ontogenetic decline in DNA synthesis; this effect was not shared by protein synthesis. In the liver, a tissue whose cells, unlike the heart, maintain the ability to divide into adulthood, there was no effect of 6-hydroxydopamine on DNA synthesis and only minor changes in protein synthesis. These results suggest that neural input provides two distinct trophic signals to the developing heart: an early promotion of cell replication associated with low levels of stimulation, and a subsequent promotion of the switchover from cell replication, to cell differentiation and enlargement, associated with high levels of stimulation. In light of the precipitous rise in circulating catecholamines at parturition, and of the subsequent development of sympathetic innervation, catecholamines are likely to play a trophic role in the establishment of the proper pattern of cardiac cell development.Abbreviations: ANCOVA,analysis of covariance;ANOVA,analysis of variance;6-OHDA,6-hydroxydopamine