OBJECTIVE We describe the levels and patterns of change in red blood cell (RBC) metallothionein (MT) during pregnancy and the neonate and relate RBCMT to other indicators of zinc and iron status. METHODS As part of a double-masked controlled trial of prenatal zinc supplementation among 242 Peruvian pregnant women, we determined RBCMT at enrollment (10-16 wk), at 28 and 36 wk of gestation, and in the cord blood at delivery in 158 women (86 who received daily supplements containing 60 mg of iron and 250 microg of folic acid and 72 whose supplements also contained 25 mg of zinc). In addition, we measured plasma and urinary zinc concentrations, hemoglobin and serum ferritin, and, on a limited sample, RBC zinc and placental MT. RESULTS RBCMT increased during pregnancy, and levels in the cord blood approximated maternal values at 36 wk. Only RBC zinc at 36 wk differed by supplement type (P < 0.05). Increases in RBCMT over pregnancy were, however, related to early pregnancy RBC zinc and inversely with the decline in plasma zinc from baseline to 36 wk of gestation. CONCLUSION Changes in RBCMT throughout pregnancy were consistent with the hypothesized role of MT in regulating zinc homeostasis. RBCMT appears to not be responsive during pregnancy to changes in zinc status achieved with supplements.