Ceramide is a widely accepted mediator of T cell apoptosis and is released upon receiving various death or stress signals. Recently we have shown that the fate of T cells, life or death, depends strictly on the strength and duration of the ceramide-generating stimulus. Subapoptotic ceramide signals were shown to negatively regulate the antigen-specific activation signaling in T cells. Here we show that these subapoptotic ceramide signals also inhibit the antigen-triggered Ca2+ signals in B lymphocytes or the FcepsilonRI-mediated response of mast cells to antigen, but in a differential manner. Burkitt B lymphoma cells, frequently used models of mature B cells, and marginal zone B cells were largely resistant to the inhibitory action of ceramide. The response to cell death-inducing (strong/long duration) ceramide stimuli, resulting in massive apoptosis in T cells, was also differential among the various immunocytes in terms of both the death mechanism and the sensitivity. Our data suggest that ceramide's effects on life and death signaling in immunocytes are cell type-/stage-specific.