The effects of intraarterially infused serotonin (5-HT) on capillary and arteriovenous anastomotic (AVA) blood flow were investigated in the hand and forearm of 19 healthy volunteers, and in the hind leg of six anesthetized pigs using radioactive microspheres with a diameter of 15 microns. The 5-HT2-receptor antagonist ketan-serin was used in an attempt to identify the receptors involved. None of the drugs in the doses used induced systemic hemodynamic effects. Low doses of 5-HT significantly increased forearm blood flow with a maximum response at the dose of 1 ng/kg/min (68 +/- 14%, p less than 0.05), whereas only at the highest dose of 80 ng/kg/min was a net decrease in forearm blood flow measured (-28 +/- 6%, p less than 0.05). Conversely, finger blood flow was not influenced by the lower doses of 5-HT, whereas a major reduction was observed at the highest dose (-90 +/- 3%). Ketanserin increased both total forearm blood flow and AVA blood flow. The drug blunted the constrictor response to 5-HT in the forearm but only slightly attenuated this response in the finger. The percentage AVA blood flow in the human hand and forearm was not influenced by an infusion of 5-HT at 80 ng/kg/min alone. However, after pretreatment with ketanserin, which itself increased the AVA component, this dose of 5-HT significantly reduced AVA flow. In the pig, total femoral blood flow was not influenced by 5-HT, but AVA blood flow was significantly reduced and capillary skin blood flow increased.(ABSTRACT TRUNCATED AT 250 WORDS)