We investigated the effects of 42 drugs on the circulation in the isolated, blood-perfused heart, kidney, small intestine, and hindlimb of rats and compared them with previously reported results in dogs. Single intra-arterial injections of drugs were made into the perfusion system of the coronary, renal, mesenteric, or femoral vascular bed. The most striking qualitative differences between rats and dogs were observed in vascular responses to nicotine, dipyridamole, 5-hydroxytryptamine (5-HT), lobeline, tetraethylammonium (TEA), and procaine. Nicotine constricted all vascular beds except the coronary bed in dogs, but dilated all four vascular beds in rats. Dipyridamole produced a dilatation in all vascular beds of rats, while it specifically constricted the renal vasculature of dogs. 5-HT constricted all vascular beds of rats, but dilated the coronary vasculature of dogs. Lobeline, TEA, and procaine constricted only the renal vascular bed in dogs, but elicited constriction of all vascular beds of rats.