Interleukin-1 and glucocorticoid hormones are the key transmitters of interaction between the neuroendocrine and immune systems. To study the molecular mechanisms of immunomodulatory effects of Interleukin-1 and glucocorticoid hormones, a search for changes in activity of neutral sphingomyelinase: the main marker of initiation of Interleukin-1beta signal transduction via the sphingomyelin pathway in target cells, was accomplished. The Interleukin-1beta was found to activate neutral sphingomyelinase both in P2 fraction of murine brain cortex and membranes of immune-competent cells. Experimental modifications of endogenous glucocorticoid level in the mouse blood were for the first time shown to induce changes in neutral sphingomyelinase activity in membranes of the cells of the immune and nervous systems. It appears that the sphingomyelinase pathway of Interleukin-1beta signaling might be a possible target for glucocorticoid hormones' immune-modulating effects.