THE Raf-1 serine/threonine kinase is a key component of the MAP kinase cascade(1-3), regulating both proliferation and commitment to cell fate(4,5). Raf activation is stimulated following its translocation to the plasma membrane, a process that ordinarily requires interaction with the membrane-localized GTPase, Ras-GTP(6-10). To investigate the mechanisms underlying Raf activation, we have developed a coumermycin-induced chemical dimerization method. We find that dimerization is by itself sufficient, in the absence of any membrane components, both to activate a modified Raf protein and to stimulate the MAP kinase cascade appropriately. As Ras-GTP-induced membrane localization increases the effective intracellular Ras concentration, our results indicate that homotypic oligomerization may ordinarily act to promote Raf activation in vivo.