The chemotherapeutic agent 5-azacytidine (5AZ) is cytotoxic via nucleic acid hypomethylation. Malformations and embryo-lethality result when rats or mice are exposed to 5AZ on any of Days 9 through 12 of pregnancy. To investigate the effect of 5AZ exposure during the pre- and early postimplantation period, we administered 0.15, 0.30, 0.60, or 1.2 mg/kg 5AZ/day to rats during Days 1-8 of pregnancy and evaluated outcome on Days 9 or 20. No adverse effects were detected on Day 9; the numbers and weights of implantation sites, the numbers of resorptions, maternal body weight gains, and hormone measures were not different from those of controls. However, when pregnancy outcome was evaluated on Day 20, dose-dependent decreases in offspring survival and fetal weight were observed and the incidences of two malformations, microphthalmia and exencephaly, were increased. (Copyright (c) 1994 Society of Toxicology.)