H uman malignant epithelial cell lines were analyzed for expression of platelet-derived growth factor (PDGF) genes. Of the 12 cell lines tested, 9, derived from breast, lung, gastric, and ovarian carcinomas, were found to express both PDGF-1 and PDGF-2 genes. The levels of both PDGF-1 and PDGF-2 transcripts were superinduced when these cells were treated with cycloheximide, an inhibitor of protein synthesis. These cells also released an activity that in studies with BALB-c/3T3 cells, inhibited binding of 125I-labeled PDGF and stimulated incorporation of [3H]thymidine. This stimulating activity was inhibited after reduction of the conditioned media by mercaptoethanol or after preincubation with antibodies to PDGF. Moreover, this activity was not affected by heat treatment. Immunoprecipitation studies revealed that breast, lung, and gastric carcinoma cells produced PDGF-like proteins that migrated as 30- and 32-kD species under nonreducing conditions and as 15- and 16-kD species under reducing conditions. In contrast, malignant cells of ovarian origin produced 14-16-kD PDGF-like proteins that were unchanged in mobility after reduction. As PDGF receptors were not detected on these malignant epithelial cells, the production of PDGF-like proteins may affect other cells in the microenvironment by paracrine mechanisms and may contribute to excessive cell proliferation, inflammatory reactions, and connective tissue remodeling seen in certain carcinomas.