The effects of histamine were studied in the maximally vasodilated gracilis muscle. Dog gracilis muscles were isolated in a plethysmograph and perfused at constant inflow pressure (102 +/- 2 mm Hg). Maximal vasodilation was produced with constant infusion of papaverine (0.2 mg/ml). Constant infusion of blood labeled with albumin-131l or red blood cells (RBC)-51Cr was made throughout the duration of the experiment. Tissue radioactivity and tissue volume changes were continuously measured. Papaverine did not increase transcapillary movement of protein, Histamine (5 microgram/kg/min) was added to the blood and 10 to 15 min later the dose level was increased to 60 microgram/kg/min. Since the vasculature was maximally dilated, changes in tissue radioactivity and tissue volume would be due to transcapillary movement rather than to vascular volume effects. The low dose of histamine significantly steepened the slopes of tissue volume and tissue albumin-s131l increase. The highest dose of histamine significantly further increased these rates. The tissue red cells-51Cr slope was not significantly increased with either dose of histamine. The capillary filtration coefficient was significantly increased above the papaverine vasodilation value by the histamine. The data would support increased transcapillary movement of proteins by other than hemodynamic mechanisms.