The industrial solvent ethylene glycol monomethyl ether (EGME) is a known teratogen that has been reported to alter calcium metabolism in guinea pigs during chronic exposure. Because of the tremendous demand of reproduction on maternal calcium stores, the effects of EGME on calcium and vitamin D metabolism during gestation were examined. Timed pregnant rats were treated by gavage with 0, 50, or 100 mg/kg EGME in 10 ml/kg distilled water on Days 9-15 of gestation (sperm = Day 1) and examined on Days 16 and 21. Virgin rats were treated for 7 days with 0 or 100 mg/kg EGME and examined 5 days later. EGME exposure did not affect body or kidney weight in virgin or pregnant rats, but liver weight was reduced in near-term pregnant rats treated with 100 mg/kg EGME. EGME (50 mg/kg) reduced litter size and fetal body weight and caused a significant number of live fetuses to have visceral abnormalities. EGME (100 mg/kg) caused all fetuses to be resorbed. In nonpregnant rats, 100 mg/kg did not affect serum 1,25-dihydroxyvitamin D (1,25(OH)2D3), 25-hydroxyvitamin D, ionic calcium, total calcium, or parathyroid hormone. EGME appeared to have a dose-dependent effect on calcium and vitamin D metabolism during gestation. On Day 21 of gestation, total calcium and ionic calcium were increased and 1,25(OH)2D3 was reduced in rats treated with EGME compared with nontreated controls. However, significant alterations in calcium homeostasis were evident only in dams that completely resorbed their litters. The changes in calcium and vitamin D metabolism during gestation appear to be secondary to the EGME-induced loss of litters.