Prenatal exposure to ethanol causes neuronal death in somatosensory cortex, but apparently not in the ventrobasal nucleus of the thalamus. Effectors such as bcl-2, bax, and caspase 3 can determine whether a neuron survives or dies. We hypothesize that ethanol differentially affects the expression of these proteins in the cortex and thalamus during the periods of naturally occurring and ethanol-induced neuronal death. Pregnant rats were fed ad libitum with an ethanol-containing liquid diet (Et) or pair-fed an isocaloric non-alcoholic diet (Ct). Samples were collected from fetuses (gestational day (G) 16 and G19) and pups (postnatal day (P) 0 through P30) and examined for bcl-2, bax, or caspase 3 expression using a quantitative immunoblotting procedure. Prenatal exposure to ethanol reduced cortical bcl-2 expression, but not bax expression on P6. Hence, the bcl-2/bax ratio was lower in Et-treated rats than in controls. In contrast, thalamic expression of neither bcl-2 nor bax was significantly different in the two groups of rats. Thus, the thalamic bcl-2/bax ratio was unaffected by exposure to ethanol. During the period of naturally occurring neuronal death, the expression of the active (20 kDa) and inactive isoforms (32 kDa) of caspase 3 was altered in the cortices of Et-treated rats, but not in their thalami. Thus, prenatal exposure to ethanol affected the early postnatal expression of death-related proteins in the cortex, but not in the thalamus. These biochemical changes concur with anatomical data on the spatial and temporal selectivity of ethanol toxicity in the developing CNS.