Imbalances of -adrenoceptor (-AR) and muscarinic ACh receptor (mAChR) input are thought to underlie perinatal cardiovascular abnormalities in conditions such as sudden infant death syndrome. Administration of isoproterenol, a ₁/₂-AR agonist, to neonatal rats on postnatal days (PN) 2-5 caused downregulation of cardiac m₂AChRs and a corresponding decrement in their control of adenylyl cyclase activity. Terbutaline, a ₂-selective agonist that crosses the placenta and the blood-brain barrier, was also effective when given either on PN 2-5 or during gestational days 17-20. Terbutaline failed to downregulate brain m₂AChRs, even though it downregulated -ARs; -ARs and m₂AChRs are located on different cell populations in the brain, but they are on the same cells in the heart. Destruction of catecholaminergic neurons with neonatal 6-hydroxydopamine upregulated cardiac but not brain m₂AChRs. These results suggest that perinatal -AR stimulation shifts cardiac receptor production away from the generation of m₂AChRs so that the development of sympathetic innervation acts as a negative modulator of cholinergic function. Accordingly, tocolytic therapy with -AR agonists may compromise the perinatal balance of adrenergic and cholinergic inputs.