The anti-metabolites, 2-methyl-3-ethyl- and 2,3-dimethyl-5-amin-oindole, given intraven., slightly raised arterial pressure and blocked the pressor but not the depressor action of serotonin in dogs and cats and prevented its respiratory-stimulant action in dogs. They had an irregular blocking action against the pressor effect of 1,1-dimethyl-4-phenyl piperazinium,iodide, tetramethyl ammonium iodide and cinobufotenine. 2-Methyl-3-ethyl-5-nitroindole given by mouth failed to block the vascular action of serotonin in normal dogs and failed to alter arterial pressure in neurogenic hypertensive dogs and in one patient with malignant hypertension. The antihistamine drugs (Benadryl, Thenfadil and Phenergan) reduced the pressor action of serotonin without diminishing the depressor in normotensive or neurogenic hypertensive dogs. In cats, the depressor action was reduced but was not correlated with reduction of response to histamine. Small doses of ergotamine reversed the pressor action of serotonin while augmenting response to other vasopressor drugs. Perfusion expts. demonstrated that ergotamine blockade was at the peripheral blood vessel. Pitressin opposes the serotonin-blocking action of ergotamine in both body and perfused extremity. Serotonin-blocking drugs were effective immediately after inac-tivation of the sympathetic nervous system but were much less so 24 hrs. after section of the spinal cord at C6. Benodaine reduced the pressor action of serotonin in normal dogs but increased it after section of the spinal cord. Priscoline slightly reduced the pressor action of serotonin but only in very large doses. Yohimbine and regitine transiently reversed the pressor action of serotonin in low doses in normal dogs but regitine was not effective after inhibition of sympathetic nervous activity. Apresoline was again found to decrease the pressor and increase the depressor response to serotonin. Drugs with a more remote structural similarity to serotonin (calycanthine, sempervirine, 5-hydroxyindole acetic acid, quinamine and serpentine) had no significant effect on vascular response to serotonin.