Blood plasma from cats, subjected to local intestinal or systemic hemorrhagic hypotension, was tested for the presence of vasoactive substances. Three assay methods were used: isolated cat vascular smooth muscle, rat uterus biossays and direct biochemical determination of serotonin (5-HT) levels. The vascular smooth muscle assay revealed vasoactive properties of the plasma and pharmacological blocking studies indicated that this vasoactivity was due mainly to the presence of 5-HT. This was confirmed in rat uterus bioassays and in biochemical assays in which similar high 5-HT levels were demonstrated whether local intestinal or systemic hypotension had been induced, suggesting that 5-HT is mainly released from the intestine. The possible relationship of this intestinal 5-HT release to the general cardiovascular derangement seen after intestinal hypotension and hemorrhagic shock is discussed.