The present study was aimed at defining the activity of human and mouse monocyte chemotactic protein-1 (MCP-1) on homologous and heterologous mononuclear phagocytes. Human natural and recombinant MCP-1 and mouse natural MCP-1/JE were tested as chemoattractants on human blood monocytes and mouse peritoneal macrophages. The human and murine cytokines were equiactive on human monocytes. Human MCP-1 was active on mouse macrophages but the maximal chemotactic effect elicited was about half that of human cells or of mouse MCP-1/JE or of reference chemoattractants. Human MCP-3, a recently identified member of the C-C chemokine family, with high sequence similarity to MCP-1/JE, was also active on mouse mononuclear phagocytes, though less so than mouse MCP-1/JE. These results caution against under-estimating the potential of MCPs when the human chemokines are applied in mice.