In the respiratory tract of the Syrian golden hamster, N-nitrosodiethylamine (NDEA) tumorigenicity is first observed on the 12th prenatal day. Thereafter, it increases with age. NDEA sensitivity coincides with cellular differentiation of the tissue and with the rapid decline of cellular proliferative activity. The hamster fetal tracheal epithelia, which have been organ cultured after transplacental pulse exposure to NDEA, develop hyperplasias, squamous metaplasias or dysplasias. These alterations occur with significantly higher frequency in the part well-differentiated at the time of exposure. Since organ culture excludes in vivo influences, these results may corroborate a closer association of tissue differentiation with prenatal NDEA sensitivity.