Involvement of the sphingomyelin cascade in Interleukin 1 beta (IL-1) signal transduction pathway in membrane fraction P2 of the murine brain cortex, was found. A key role of the membrane enzyme neutral sphingomyelinase (nSMase) in triggering the sphingomyelin pathway for IL-1 beta, was confirmed. The IL-1 beta was shown to activate in a dose-dependent manner nSMase in the P2 fraction of the brain cortex. Employment of both brain cortex membranes from the mice deficient in the type I IL-1 receptor and of IL-1 receptor antagonist made it possible to obtain evidence on the necessity of the IL-1 beta binding to the type I IL-1 receptor for the nSMase activation. It appears that the IL-1 beta effects on the CNS are realized via IL-1 receptor type I and activation of the nSMase as an initiating enzyme of the sphingomyelin cascade.