The authors have demonstrated that human interleukin-4 (IL-4) induces increased expression of the mRNA encoding the monocyte-specific chemoattractant and activator, MCP-1/JE, in human endothelial cells (EC). In addition, treatment of ECs with IL-4 resulted in the synthesis and secretion of MCP-1/JE protein. While IL-4 did not significantly influence the induced expression of MCP-1/JE mRNA by interleukin-1 (IL-1) or tumor necrosis factor, concomitant treatment with IL-4 and IL-1 caused more secretion of MCP-1/JE protein than either cytokine alone. These results suggest that EC-produced MCP-1/JE may mediate some of IL-4's effects on monocyte physiology in vivo, including IL-4's anti-tumor properties.