To investigate the role of SH-2-containing pro- tein tyrosine phosphatase 1, SHP-1, in IL-4-induced IL-4 receptor (IL-4R) expression, we examined IL-4 receptor α-chain (IL-4Rα) mRNA expression in Na3VO4-treated wild type (WT) spleen cells and measured IL-4R mRNA in IL-4-stimulated spleen cells of viable motheaten mice (mev/mev). It is found that IL-4-induced IL-4R mRNA ex- pression was impaired in Na3VO4-treated WT spleen cells and IL-4-stimulated mev/mev spleen cells. Here we show that the impaired IL-4-induced IL-4Rα mRNA expression was due to reduced expression of IL-4R that led to impaired STAT6 signaling. We further demonstrate that reduction of IL-4Rα protein expression in mev/mev spleen cells was due to alteration in cell compositions. In mev/mev spleen, the per- centages of CD4+, CD8+, and CD19+ cells expressing rela- tively high levels of IL-4R were reduced dramatically while the percentages of Mac-1+ and Gr-1+ cells with relative low levels of IL-4R increased greatly. Despite the profound effect of reduced expression of IL-4R protein, the IL-4Rα mRNA expression was comparable in spleen cells of littermate con- trol mice (+/?) and mev/mev mice and no differences were found in B cells, T cells, and macrophages, suggesting cell type-specific downregulation of IL-4R expression in macro- phages through a posttranscriptional mechanism. Our study suggests that SHP-1 is required for IL-4-meidated function and indirectly regulates IL-4-meidated function in spleen cells by affecting hematopoiesis. To investigate the role of SH-2-containing pro-tein tyrosine phosphatase 1, SHP-1, in IL-4-induced IL-4 receptor 4Rα) mRNA expression in Na3VO4-treated wild type (WT) spleen cells and measured IL-4R mRNA in IL-4-stimulated spleen cells of viable mothe mice (mev / mev) 4R mRNA ex- pression was impaired in Na3VO4-treated WT spleen cells and IL-4-stimulated mev / mev spleen cells. Here we show that the impaired IL-4-induced IL-4Rα mRNA expression was due to reduced expression of IL- 4R that led to impaired STAT6 signaling. We further demonstrate that reduction of IL-4Rα protein expression in mev / mev spleen cells was due to alteration in cell compositions. In mev / mev spleen, the per- centages of CD4 +, CD8 +, and CD19 + cells expressing rela- tively high levels of IL-4R were reduced dramatically while the percentages of Mac-1 + and Gr-1 + cells with relative low levels of IL-4R increased greatly. Des pite the profound effect of reduced expression of IL-4R protein, the IL-4Rα mRNA expression was comparable in spleen cells of littermate con- trol mice (+ /?) and mev / mev mice and no differences were found in B cells, T cells, and macrophages, suggesting cell type-specific downregulation of IL-4R expression in macro-phages through a posttranscriptional mechanism. Our study suggests that SHP-1 is required for IL-4-meidated function and indirectly regulates IL-4-meidated function in spleen cells by affecting hematopoiesis.