Some of cocaine (COC)'s pathophysiological effects on exposed embryos likely result from its vasoconstrictive action, and serotonin2 (5-HT2) agonists such as dimethoxyiodophenylaminopropane (DOI) can mimic these effects. Infusions of COC (5 mg/kg/min) or DOI (0.5 mg/kg/min) for 15 min into chicken eggs with embryos on E15 caused a significant reduction in blood vessel diameters (14 and 30%, respectively). Pretreatment with the 5-HT2 antagonist ritanserin (RIT, 0.9 mg/kg) 18-22 h earlier blocked the effect of COC and blocked or attenuated the effect of DOI. In separate groups of chicken embryos exposed to multiple injections of low doses of COC on E18, herniated umbilici were prominent in hatchlings. A single bolus injection of the same absolute amount of COC did not cause herniated umbilici. An additional experiment replicated the induction of herniated umbilici by multiple injections of COC and demonstrated the probable involvement of 5-HT2 receptors because RIT blocked COC's ability to induce this anomaly. These data suggest that COC's vasoconstrictive effect, via 5-HT2 receptors, may play a mechanistic role in some adverse outcomes in embryos exposed to COC.