The aim of this study was to determine whether the glutamine analog, 6-diazo-5-oxo-L-norleucine (DON), which is known to inhibit cell degeneration in rat palatal processes in vitro, exerted a similar effect on cleft palatal processes in vivo. Sprague-Dawley rats were injected intraperitoneally with 5.0 mg/kg body wt of DON on Day 15 of gestation and fetuses were removed over Days 16, 17 and 18. A high frequency (80-90%) of cleft palate was obtained. Fetal heads were removed on each of the three days and transverse sections of the palatal processes were examined by light and electron microscopy. Results showed that treatment with DON failed to inhibit degenerative changes in the palatal epithelium. The same sequence and timing of ultrastructural changes occurred in the expected fusion zone (EFZ) as have been described previously in cleft palatal processes from Meclozine-treated and amniotic sac punctured rat fetuses; namely, autophagic cytoplasmic degeneration, loss of basal lamina and the subepithelial accumulation of macrophages all of which were most prominent in that part of the EFZ immediately next to the developing oral epithelium. The results therefore suggest that a teratogenic dose of DON does not interfere with the ultrastructurally observable changes in the EFZ.