Dobutamine, a recently synthesized catecholamine, was developed as an agent which would produce increased inotropy in low cardiac output states without major changes in heart rate, cardiac rhythm, or peripheral vascular resistance. However, the effect of dobutamine on the capacitance vasculature is unknown. Since alterations of systemic vascular capacity influence venous return and hence cardiac output, we performed the present study. The muscular capsules of the canine spleen make them representative of the capacitance vasculature. We weighed exteriorized canine spleens continuously in 26 anesthetized dogs. Dobutamine infused for 15 minutes at 4 and 16 μg/kg per min was associated with decreases in splenic weight of 15 ± 2% (SEM) (P< 0.0005) and 33 ± 2% (P< 0.0001) from controls of 249 ± 27 g and 313 ± 42 g. Dobutamine-induced splenic contraction was abolished by phenoxybenzamine but not by propranolol. Injections of dobutamine into the splenic artery produced significant decreases in splenic weight without any change in systemic hemodynamics. In six additional dogs with ganglionic blockade and supported by total cardiopulmonary bypass, decreases or increases in vascular volume were recorded as changes in oxygenator volume. Dobutamine infusion at 30 μg/kg per min for 10 to 24 minutes in these dogs was associated with decreases in vascular volume of 259 ± 28 ml (P< 0.0001). Selective blockade revealed the dobutamine effect to be mediated by α-adrenergic receptor stimulation alone. Thus, in the intact animal, the administration of dobutamine should increase venous return and hence cardiac output through an α-adrenergic-mediated decrease in systemic vascular capacity. Circ Res 46:133-138, 1980