In helically cut stips of cerebral, coronary, mesenteric, and renal arteries from dogs, a test solution containing hemoglobin (Hb) and soluble constituents, obtained by exposure of blood clot to distilled water, produced a dose-related contraction. The contraction of cerebral arteries was greater than that of the other arteries. Methemoglobin (metHb) caused only a slight contraction. The contractile response of cerebral arteries to the Hb-containing test solution was attenuated by aspirin (10(-5) to 2 X 10(-4) M), polypholretin phosphate (PPP, 3 X 10(-5) gm/ml), a prostaglandin (PG) antagonist, and cinanserin (10(-7) M), a serotonin antagonist. Combined treatment with these antagonists suppressed the response to the test solution, but only slightly attenuated contractions induced by K+. Phentolamine was ineffective. Contractions of measenteric arterial strips induced by the test solution were potentiated by aspirin, but were attenuated by PPP and cinanserin. Serum also produced contractions of cerebral and mesenteric arteries, which were attenuated by treatment with cinanserin or PPP. Contractile responses to Hb-containing solution and serum obtained from dogs pretreated with reserpine were weaker than those to the solutions obtained from control dogs. It may be concluded that the Hb-containing test solution releases vasoconstricting PG's from the cerebral arterial wall but vasodilating PG's from mesenteric arteries. The test solution appears to contain vasconstricting PG's and serotonin. Serum-induced contractions appear to be mediated mainly by serotonin.