The macrophage has been suggested to be responsible for the connective tissue cell proliferation that accompanies most chronic inflammatory responses. One of the secretory products of activated macrophages is MDGF, a growth factor (or factors) for fibroblasts, 3T3 cells, smooth muscle, and vascular endothelium. This report demonstrates that a significant portion of the mitogenic activity for 3T3 cells secreted by cultured human alveolar and peritoneal macrophages is due to a molecule (or molecules) similar to platelet-derived growth factor (PDGF). Two size classes (approximately 37,000-39,000 and 12,000-17,000 daltons) of mitogenically active PDGF-like molecules are detected by two criteria--antigenic similarity with PDGF and ability to compete with 125I-PDGF for high-affinity binding to the PDGF receptor. The presence of mRNA for the B chain of PDGF is demonstrated by Northern analysis, and de novo synthesis of these molecules by activated macrophages is shown by immunoprecipitation of 35S-labeled proteins with anti-PDGF IgG.