In view of the common practice of dieting for weight reduction, the influence of severe food restriction (about 25% of ad libitum intake) on adrenergic mechanisms was studied. Cardiac norepinephrine and epinephrine concentrations as well as plasma norepinephrine levels, were increased upon feeding a restricted diet to rats for 14 days in comparison with control rats that ingested about 30 g food/ day. Bradycardia as well as characteristic electrocardiographic abnormalities, including prolongation of the QRS and QT intervals, were observed in food-restricted rats. Dietrestricted rats did not develop ventricular arrhythmias in response to epinephrine injections as readily as control rats. Depression in both + dP/dt and -dP/dt of the heart in situ as well as reductions in the inotropic responses to epinephrine were evident in diet-restricted rats. Beta-adrenergic binding studies revealed a significant decrease in receptor density, but the dissociation constant for binding was also depressed in the food-restricted rat heart. Downregulation of the beta-adrenergic receptors in the heart may explain the lack of an epinephrine-induced increase in contractile force development as well as arrhythmias in food-restricted rats. These data demonstrate that severe food restriction has marked effects on adrenergic mechanisms and heart function, and thus some caution should be exercised at early periods of this therapy for weight reduction.