This report describes the effects of low levels of copper, nickel and lead salts on the concentrations of alpha-fetoprotein (AFP) in the sera and amniotic fluid of pregnant Nylar mice. During the early and mid-gestation (9-17 days), pregnant mice were injected intraperitoneally twice with heavy-metal salt solutions and were autopsied two days following the second injection. Maternal sera and amniotic fluid (AF) were collected and AFP levels were quantified by radial immunodiffusion. Metal levels determined by X-ray fluorescence spectroscopy in individual samples confirmed the presence of trace metals in the fetus. Low doses of nickel and copper were associated with elevated AFP levels in amniotic fluid in 15-17 day pregnant animals, while maternal serum AFP levels mostly remained unchanged. Decreased concentrations of maternal serum AFP occurred with increased doses of copper and lead in contrast to elevated concentrations of AFP in amniotic fluid. Furthermore, there was an increase in fetal wastage when higher doses of copper and lead were administered. A reduction of secondary litter size (F1 generation) with low dosage levels of lead was also observed. These results imply that the fetal-maternal transfer of AFP may either be impaired or reflect increased leakage or decreased placental permeability in the presence of sublethal doses of copper and lead. These findings suggest that the parallel measurements of AFP concentrations in sera and amniotic fluid might be employed for assessment of embryo- and fetotoxicity when heavy metal intake is suspected during pregnancy.