A new member of the mitogen-activated protein kinase family, alternatively termed CSBP, p38, or RK, has been identified independently by several laboratories recently. Activation of this novel protein kinase via dual phosphorylation has been observed in different cell systems upon stimulation by a wide spectrum of stimuli, such as physicochemical stress and treatment with lipopolysaccharide or proinflammatory cytokines such as interleukin-1 and tumor necrosis factor. Furthermore, CSAID cytokine biosynthesis inhibitors have now been determined to be potent and selective inhibitors of CSBP/p38/RK kinase activity. These inhibitors will help to dissect signaling pathways involved in inflammatory responses. In particular, for the first time a definitive signal transduction pathway can be prescribed to the action of lipopolysaccharide in cytokine production in macrophages.