A ubiquitously expressed, large (864 aa) mouse membrane glycoprotein has been cloned after its binding to soluble vIL-17+Fc fusion protein. This receptor, which also binds CTLA-8, is unrelated to previously identified cytokine receptor families. The cDNA encoding a human homolog of the mIL-17R has been isolated by crosshybridization. Like its mouse counterpart, the human IL-17R (866 aa) is also ubiquitously expressed. Monoclonal antibodies against the hIL-17R block the secretion by fibroblasts of IL-6 induced by hIL-17+Fc. Binding studies, dose+ response, and cellular restriction of IL-17 biological activities suggest the existence of another, as yet unidentified, high-affinity IL-17R chain.