The physiological and behavioral effects of embryonic exposure to ethanol and cocaine, given during active neurogenesis (embryonic days E3 and E4), were studied in 1- and 2-day-old chicks. Broiler chicks (n = 131) from five embryonic treatment conditions were tested: incubative controls (n = 28), vehicle (saline plus 50 micrograms/ml bacitracin; n = 27), 10 mg ethanol (n = 20), 150 micrograms cocaine (n = 25), or co-drug (10 mg ethanol and 150 micrograms cocaine; n = 31). Compared with controls, embryo mortality for the cocaine alone embryos was significantly increased. No significant embryonic treatment effects among chicks were found for hatching times, body weights at hatch and testing, and temperature regulation when cold stressed. Behaviorally, chicks were first trained to key-peck for heat/light reward (autoshaping). Chicks in all groups increased responding from autoshape session 1 to session 2 (24 trials/session). In an acquisition-extinction session (12 trials/phase), chicks in all groups except those in the co-drug group decreased responding from acquisition to extinction. In a second acquisition-extinction session following a drug challenge of 0.5 mg/kg apomorphine, chicks in all embryonic treatment groups showed enhanced responding. Hence, in those chicks that survived, the selected doses of ethanol and cocaine produced minimal physiological and behavioral effects individually, but when given together did produce a significant deficit in extinction responding.