The contractile properties and contractile protein enzymatic activity of skeletal muscle can be altered by neural influences. To determine whether similar influences apply to cardiac muscle, adult rats were chemically sympathectomized by intravenous injection of 6-hydroxydopamine (6-OHDA). After 2 weeks of treatment, rats were anesthetized and an index of myocardial contractility (max dP/dt) was measured in situ. Max dP/dt was depressed in 6-OHDA-treated rats [4560 +/- 420 (mean +/- SE) mm Hg/sec] when compared to controls (6710 +/- 580 mm Hg/sec). Sympathectomy was verified by reduced hemodynamic responsiveness to tyramine injections. After functional measurements had been completed, the heart was excised. Myofibrils were prepared from left ventricular tissue and analyzed for ATPase activity. Myofibrillar protein yield averaged 38 +/- 2 mg/g in controls and was not significantly different in 6-OHDA rats. Myofibrillar ATPase activity was 0.314 +/- 0.014 mumol P1/mg per min in controls. Enzyme activity was significantly reduced to 0.230 +/- 0.020 mumol P1/mg per min in 6-OHDA rats. The results demonstrate that a chronic reduction in sympathetic stimulation to the heart results in a depression of an index of myocardial contractile function which is accompanied by reduced myofibrillar ATPase activity. Acute (16-18 hours) chemical sympathectomy depressed the contractile function index without altering ATPase activity. Bilateral adrenalectomy produced no further decrement in myofibrillar ATPase activity in chronically (2 weeks) sympathectomized rats. Therefore, it appears that the changes in contractile protein enzymatic properties are mediated by sympathetic neural influences and may involve the synthesis of new contractile protein(s) with altered enzymatic properties.