The hypothesis that hepatic metallothionein (MT) induction in the pregnant animal results in a Zn deficiency in the embryo was tested by treating pregnant rats with alpha-hederin, reported to induce MT in rat liver. Morphological development was assessed in term fetuses. A single dose of alpha-hederin, of 3-300 micromoles/kg, caused a dosage-related increase in maternal hepatic MT. Maximum induction was 11-15-fold greater than control and occurred at dosages of 30 micromoles/kg and higher. (Zn) concentration in liver and liver cytosol increased along with MT, reaching a maximum at dosages of 30 micromoles/kg and higher. Plasma (Zn) decreased after alpha-hederin treatment to a level approximately 75% of control at 30 micromoles/kg and 50% of control at 300 micromoles/kg. Zn distribution was evaluated by giving a (65)Zn 8 hours after treatment and measuring (65)Zn 10 hr later. Both 30 and 300 micromoles/kg increased resorptions, and 300 micromoles/kg decreased fetal weight and increased the incidence of abnormal fetuses. These data support the hypothesis that systemic changes in Zn status, brought about by induction of hepatic MT, may be a mechanism for maternally-mediated abnormal development.