The effect of ethanol infusion upon placental uptake of amino acids was studied in pregnant sheep. Blood ethanol levels of 150-260 mg/dl obliterated the normal uptake of amino acids by the in vivo placenta. However, when human placental villi were incubated in vitro with ethanol at 300 mg/dl, there was no inhibition of uptake of 14C alpha-amino isobutyric acid (AIB). In contrast, 2-20 mM, but not 50 or 200 micro M, acetaldehyde significantly inhibited AIB uptake (% inhibition at 90 min: 2 mM, 23.5 +/- 9.6%; 5 mM, 33.8 +/- 4.7%; 10 mM, 54.6 +/- 2.9%; 20 mM, 61.5 +/- 7.5%; p less than 0.01 for all 4 concentrations). When human placental villi were preincubated with 10 micro M acetaldehyde, washed, and incubated with 14C-AIB in the absence of acetaldehyde, there was significant residual inhibition of AIB uptake. The data suggest that ethanol-associated placental injury may contribute to the pathophysiology of the fetal alcohol syndrome.