Systemic vascular effects of dopamine, dobutamine, and prenalterol were studied in 45 anesthetized open-chest dogs. Blood flow (Q) and right atrial pressure (Pra) were independently controlled by a right heart bypass. Transient changes in central blood volume after an acute reduction in Pra at a constant Q showed that blood was draining from two vascular compartments with different time constants, one fast and the other slow. Dopamine (2.5-10 micrograms X kg-1 X min-1) was the most active drug with dose-related increases in heart rate 6-19%, arterial pressure (Pa) 3-36%, and venous compliance 2-25%. Small doses of dopamine (2.5 and 5 micrograms X kg-1 X min-1) reduced arterial resistance of the slow time-constant compartment increasing Q distribution to that compartment 21-42%, whereas larger doses increased both arterial resistance and venous compliance in that compartment. Arterial resistance in the fast time-constant compartment increased with all doses of dopamine. Dobutamine (2.5-10 micrograms X kg-1 X min-1) modestly increased heart rate 2-11% and Pa 9-12% without altering Q distribution demonstrating a relatively flat dose response. Dobutamine 2.5-5 micrograms X kg-1 X min-1 increased venous compliance 5-10% while 10 micrograms X kg-1 X min-1 had no effect or decreased compliance of both compartments. Prenalterol 3 micrograms X kg-1 X min-1 increased Pa 9% primarily by increasing arterial resistance in the fast time-constant compartment without altering heart rate or blood flow distribution. Doses of prenalterol 10-100 times greater caused dose-dependent reductions in Pa and vascular compliance. In this animal model of the circulation with a fixed cardiac output, dopamine had the greatest effect on the peripheral vasculature and chronotropy.