The role of monocyte chemoattractant protein‐1 (MCP‐1) in the recruitment of blood‐derived monocytes in a model of zymosan peritoneal inflammation was investigated. After zymosan injection (1 mg) a rapid influx of polymorphonuclear leukocytes (PMN) and monocytes into the peritoneal cavity associated with mouse MCP‐1 (JE) gene activation and protein secretion in the exudates occurred. MCP‐1 production (maximal at 4 h) preceded the accumulation of monocytes (F4/80‐positive cells, maximally recovered between 16 and 24 h). Treatment of mice with a single injection of anti‐mouse MCP‐1 antibody inhibited 16‐h monocyte accumulation by ~40%, however, a significant decrease in the number of PMN was also measured. Finally, intraperitoneal injection of murine recombinant MCP‐1 (1 μg) produced a selective accumulation of monocytes (F4/80‐positive cells) into the peritoneal cavity. In conclusion, we show the novel existence of a strict relationship between MCP‐1 production and leukocyte accumulation in this model of acute inflammation. J. Leukoc. Biol. 63: 108–116; 1998.