&NA;The development of cardiac hypertrophy is associated with marked changes in cardiac autonomic innervation. Significant and sustained reductions of myocardial catecholamine stores and activities of tyrosine hydroxylase and dopamine &bgr;‐hydroxylase have been reported in models of acutely induced ventricular hypertrophy. Conversely, activity of choline acetyltransferase, a marker of parasympathetic nervous function, shows transient increases during the development of acute right ventricular hypertrophy. The potential physiological importance of these changes prompted us to examine a clinically more relevant model of slowly progressive ventricular hypertrophy. Application of a loose band around the pulmonary artery of weanling guinea pigs resulted in a growth‐related progressive right ventricular pressure overload. Right ventricular weight‐to‐body‐weight ratio was increased significantly and progressively at 9 and 18 weeks in banded animals (0.92 ± 0.05 and 1.31 ± 0.11 mg/g, respectively,p<0.01) compared with sham‐operated controls (0.55 ± 0.02 and 0.59 ± 0.01 mg/g, respectively) but showed no further gain at 27 weeks (1.41 ± 0.10 mg/g). Activities of tyrosine hydroxylase and dopamine &bgr;‐hydroxylase remained unchanged in all experiment groups, while right ventricular contents of norepinephrine in banded animals at 18 and 27 weeks exhibited sustained and progressive increases (2.45 ± 0.11 and 3.40 ± 0.19 μg/right ventricle, respectively) over controls (1.80 ± 0.13 and 2.40 ± 0.22 μg/right ventricle, respectively,p<0.01). The activity of choline acetyl‐transferase was markedly elevated in banded animals at 18 weeks (32.6 ± 2.7 nmol/hr/right ventricle) but returned to baseline by 27 weeks (22.8 ± 1.4 nmol/hr/right ventricle). We conclude that the time course of pressure overload is an important variable influencing sympathetic neural indexes in the hypertrophied heart. Thus, in contrast to acutely induced right ventricular hypertrophy, markers of sympathetic innervation may be preserved in severe cardiac hypertrophy provided it develops in a physiological, gradual fashion. On the other hand, transient increases of the cardiac parasympathetic marker appear to be a common feature of the development of myocardial hypertrophy produced by either acute or chronic progressive pressure overload. Our observations suggest that sympathetic‐parasympathetic interactions may vary during the development of chronic progressive cardiac hypertrophy and that these interactions may differ in chronic progressive and acute ventricular hypertrophy. (Circulation Research1987;61:55‐62)