The effect of prednisolone on the kinetics of killing of Detroit-6 cells by rat lymphocytes has been studied utilizing the release of 51Cr as a measure of target cell death. The results show that in both killing by allergized lymphocytes, and killing of antibody coated target cells by normal lymphocytes, there is a short (less than 15 min) prednisolone-sensitive induction phase. Prednisolone has no effect on the reaction after this phase. The inhibition of induction by prednisolone appears to have two mechanisms. The first occurs rapidly following the addition of the drug to the cells, and must involve a primary action of prednisolone. Washing the cells free of prednisolone allows initiation, and killing can proceed almost normally, but if these washed cells are preincubated before mixing with target cells, then a secondary inhibition of induction develops progressively.