The mechanisms underlying the inhibition of T-cell proliferation by methylprednisolone (MPS) have been investigated using a T-cell colony assay. Cell fractionation experiments have demonstrated that MPS exerted its effects at the level of both T-cells and monocytes. Thus, monocytes treated with MPS released a soluble factor that had suppressor activity on T-cell proliferation. Moreover, MPS directly blocked the proliferative capacity of T-cells, as demonstrated by the finding that MPS-treated T-cells formed reduced numbers of colonies even under optimal culture conditions and in the presence of exogenous IL-2.