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THE induction of programmed cell death, or apoptosis, involves activation of a signalling system, many elements of which remain unknown¹. The sphingomyelin pathway, initiated by hydrolysis of the phospholipid sphingomyelin in the cell membrane to generate the second messenger ceramide^2,3, is thought to mediate apoptosis in response to tumour-necrosis factor (TNF)-α^2,3, to Fas ligand⁴ and to X-rays⁵. It is not known whether it plays a role in the stimulation of other forms of stress-induced apoptosis. Given that environmental stresses also stimulate a stress-activated protein kinase (SAPK/JNK) ^6–12, the sphingomyelin and SAPK/ JNK signalling systems may be coordinated in induction of apoptosis. Here we report that ceramide initiates apoptosis through the SAPK cascade and provide evidence for a signalling mechanism that integrates cytokine- and stress-activated apoptosis.