Monocyte chemotactic protein (MCP)‐1 and MCP‐2, two closely related CC chemokines, are important mediators of monocyte and lymphocyte migration. These chemokines are secreted by various normal cell types, including fibroblasts, epithelial cells, and leukocytes, as well as by tumor cells. After stimulation with different cytokines and cytokine inducers the MCP‐2 production levels are always lower than those of MCP‐1. In human diploid fibroblasts cytokines differentially regulate chemokine induction, interleukin (IL)‐1β and interferon (IFN)‐γ being potent stimuli of MCP‐1 and MCP‐2, respectively. Co‐stimulation of fibroblasts by 10 U/mL IL‐1β and 20 ng/mL IFN‐γ resulted in a synergistic induction of MCP‐2, whereas the combined effect on MCP‐1 and IL‐6 production was rather additive. These findings were confirmed at the mRNA level by Northern blot analysis. In contrast, in human MG‐63 fibroblastoid cells and HEp‐2 epithelial cells, selected for their poor responsiveness to IL‐1β and IFN‐γ, MCP‐2 as well as MCP‐1 and IL‐6 were synergistically induced, yielding protein levels that were increased 3‐ to 30‐fold above the additive levels. When IFN‐β was used as a co‐stimulant of IL‐1β, a similar synergistic induction of MCP‐1 and MCP‐2 was measured both at the protein and the mRNA level. It can be concluded that, when synergy occurred, the MCP‐1 and MCP‐2 expression levels reached a comparable maximum, indicative for an equal contribution of these chemokines in normal and pathological conditions. J. Leukoc. Biol. 63: 364–372; 1998.