We have investigated the effect of prenatal exposure to ethanol on the extent of binding and surface distribution of the lectin concanavalin A (con A) on rat cortical astrocytes during the periods of proliferation and differentiation in primary culture. The enzymatic activity of the plasma membrane glycoprotein 5'-nucleotidase was also assessed. The cells were obtained from control fetuses (no exposure to ethanol) and from fetuses prenatally exposed to ethanol. The main findings were: 1) both proliferating and differentiating control astrocytes showed two distinct types of surface con A receptors that could correspond to high- and low-affinity binding sites; 2) the extent of con A binding was greater in mature than in proliferating control cells; 3) the distribution of con A on cell surface components changed with differentiation; 4) the activity of 5'-nucleotidase showed a substantial increment during the period of differentiation; and 5) prenatal exposure to ethanol clearly decreased the ability of astrocytes to bind con A, altered the surface distribution of the receptors for this lectin, and decreased the activity of 5'-nucleotidase. These effects were more marked in proliferating cells. In conclusion, it is shown that the extent of con A labeling and the activity of 5'-nucleotidase in astrocytes are dependent on the stage of cell differentiation and that prenatal exposure to ethanol alters the plasma membrane structure of these cells during development.