Selective pressure overload of the right ventricle in guinea pigs resulted in early and sustained reductions in tyrosine hydroxylase and dopamine-beta-hydroxylase activities in the right ventricle. No changes in tyrosine hydroxylase activity were detected in stellate ganglia sinoatrial (SA) nodal region, atrioventricular (AV) nodal region, or left ventricle. Reductions in tyrosine hydroxylase activity in stressed right ventricle were similar regardless of duration of pulmonary artery constriction, extent of hypertrophy, presence or absence of hepatic congestion, and preservation or depletion of catecholamines. The changes may represent localized loss of sympathetic nerve fibers; factors involved directly in the process of pressure-overload-induced hypertrophy may be responsible. However, sympathetic nerves remaining in hypertrophied ventricle respond normally to cold-induced sympathetic activation. The reduction in tyrosine hydroxylase activity and the maintenance of norepinephrine turnover in residual innervation to hypertrophied right ventricle support the concept that sympathetic neural regulation of hypertrophied cardiac tissue is altered but not lost.