A developmental toxicity study was conducted with 1,6-hexamethylene diisocyanate (HDI), in the Sprague-Dawley rat. Inseminated rats were exposed to concentrations of 0, 0.005, 0.050, or 0.300 ppm HDI via inhalation (whole body exposure) on days 0 through 19 of gestation. Maternal toxicity, as demonstrated by clinical signs and changes in body weight gain during gestation, was characterized. Dams were sacrificed on gestation day 20, at which time fetuses were removed by cesarean section, the uterus was examined, and a gross maternal necropsy was performed. Maternal evaluation also included lung weight and a detailed histopathologic assessment of the nasal turbinates, larynx, trachea, and lungs. All fetuses were evaluated for external anomalies. Approximately half of each litter was examined for visceral effects, the other half underwent a skeletal (bone and cartilage) examination. Maternal toxicity was demonstrated in the 0.300 and to a lesser extent in the 0.050 ppm exposure groups. No maternal effects were noted in the 0.005 ppm dose group. Test compound-related maternal effects were restricted to histopathological findings, and included acanthosis, hyperkeratosis, inflammation of the nasal turbinates, and more seriously, degeneration of the olfactory epithelium. No pathological alterations were noted in the larynx, trachea, or lungs in any dose group. No test compound-related effects were observed on any reproductive parameters, or any embryonic endpoints, including pre/post-implantation loss and resorptions. There were no effects on litter size or the number of fetuses per implantation site and no effects on fetal or placental weights were observed. No test compound-related fetal external, visceral, or skeletal findings were observed. No effect on the fetal or litter incidence of total malformations or variations was observed and there was no difference in the incidence of malformations between males and females. 1,6-Hexamethylene diisocyanate (HDI), administered as described in this study, produced maternal effects (nasal turbinate histopathology) at concentrations of 0.050 and 0.300 ppm. No developmental toxicity was observed at any concentration level. Therefore, the maternal no-observed-effect-level (NOEL) was 0.005 ppm HDI and the developmental NOEL was 0.300 ppm HDI.