Concentrations of methylprednisolone which have lethal effects on human lymphoblastoid cell lines in vitro cause a reduction both in the uptake of uridine and thymidine into acid-soluble material and their incorporation into acid-insoluble material. These effects are virtually instantaneous, which indicates that they do not depend on alterations in gene activity. Normal uptake of nucleosides into cells is by both simple and facilitated diffusion, and methylprednisolone appears to act directly on the cell surface to inhibit only facilitated diffusion uptake.