We describe here the characterization of the interleukin (IL) 13 receptor and a comparison with the IL-4 receptor on different cell types. Several, but not all, of the IL-4 receptor-positive cells showed specific IL-13 binding, which was always completely displaced by IL-4. In the IL-13 receptor-positive cells, the IL-13 either completely or partially displaced the labeled IL-4. Further characterization of the IL-13 receptor in two cell lines, COS-3 and A431, representative of the groups of complete and partial displacement of IL-4 by IL-13, respectively, showed that the IL-13 binds with high affinity (Kd approximately 300 pM) to both cells and that the number of binding sites is, in COS-3 cells, equivalent to that for IL-4 and, in A431 cells, is smaller than that for IL-4. Cross-linking of labeled IL-13 yielded, on COS-3 cells, two affinity-labeled complexes of 220 and 70 kDa, and on A431 cells, one complex of 70 kDa; labeled IL-4 yielded on both cells the same pattern of three complexes of 220, 145, and 70 kDa. Altogether, these results suggest that the IL-13 receptor may be constituted by a subset of the IL-4 receptor complex associated with at least one additional protein.