The effects of glucocorticoids on lymphoid cell growth and thymidine incorporation into DNA were studied using the S49 mouse lymphoma cell line. Glucocorticoid-mediated lymphocytolysis in these cells is preceded by an arrest in the G1 phase of the cell cycle [1]. However, this arrest is only partial, and is reversible by washing out the hormone. Thus, although the overall impression is that these cells are arrested in G1 and then begin to die, they apparently can escape the arrest and proceed through the cell cycle, albeit at a relatively low level. The mode of DNA synthesis in these glucocorticoid-treated cells is replicative and not repair. The importance of the inhibition of thymidine incorporation to the cell death process in S49 cells is evident from experiments in which cells are treated with both the hormone and various DNA synthesis inhibitors; a synergistic killing of the cells is obtained. Thus, the inhibition of DNA synthesis and cell proliferation is a rapid, and perhaps primary effect of glucocorticoids on the complex process of hormone-mediated lymphocytolysis in this mouse cell line.