The isotope washout method has been widely used to study characteristics of the microcirculation in localized vascular beds. Some of these studies have used local injections of vasodilating agents to maximally dilate the vascular bed. This study was undertaken to determine the agent most effective in producing this critical vasodilation. A rabbit model was constructed that allowed the study of the subcutaneous blood flow by either 133Xe and 131I-antipyrine washout. Dose-response curves were constructed for five agents. The agents used and the doses that produced the maximum washout rate, were histamine (100 micrograms), verapamil (0.5 mg), prostaglandin E1 (6 micrograms), papaverine (5 mg) and nitroprusside (60 micrograms). The five agents at these doses were compared with each other, and nitroprusside produced a greater washout rate than papaverine (P less than 0.005), histamine (P less than 0.001) and verapamil (P less than 0.005). There was no difference between nitroprusside and prostaglandin E1 (P greater than 0.01). The effect of three of the agents in producing tissue oedema was examined by comparing the washout rates values obtained with the two isotopes. Both nitroprusside and papaverine produced large oedema whereas histamine resulted in little oedema formation. Nitroprusside, therefore, appears to be the most suitable vasodilating agent for use in studies which require maximum vasodilation of localized vascular beds.