The glucose concentration in growth medium has been shown to regulate the number of sodium-coupled glucose transporters in LLC-PK(i) epithelial cells. Epithelia grown in high concentrations of glucose express fewer transporters than epithelia grown in low concentrations of glucose. In the present work, the effect of a dose of ionizing radiation sufficient to block the incorporation of thymidine was examined in order to gauge the importance of cell replication in the hexose transport regulatory process. The low rate of thymidine incorporation in the plateau phase was completely eliminated by ionizing radiation. Under conditions of irradiation that completely blocked thymidine incorporation, down-regulation, namely the loss of α-methylglucoside-concentrating capacity, brought about by switching the epithelium from low to high glucose-containing medium, is independent of the irradiation and therefore most likely is also independent of cell replication. In contrast, the up-regulatory phenomenon is strongly impaired by radiation. This impairment may be due to specific radiation impairment of gene expression necessary for the up-regulatory process. It is apparent from the dose-response data that up-regulation is not inhibited by irradiation in a simple manner and is not inhibited at the same radiation dose as cell replication.