The authors tested the hypothesis that the B chain of the platelet-derived growth factor (PDGF), a known connective tissue mitogen and growth factor, could be expressed by human soft tissue tumors, and that its expression could play a role in the control of cell proliferation in these tumors. Using a set of 56 soft tissue tumors, including benign tumors and all three grades of sarcomas, PDGF-B chain protein was localized using immunohistochemistry and PDGF-B mRNA was localized using in situ hybridization. The hypothesis that PDGF-B expression was related to cell proliferation was tested by simultaneously demonstrating the expression of the proliferating cell nuclear antigen in sequential tissue sections of the same tumors. Sixty and 82% of tumors had demonstrable PDGF-B mRNA and protein, respectively, with a strong correlation between their degrees of expression (P = 0.0001). Among the sarcomas, a strong correlation between PDGF-B expression and increasing malignant tumor grade (P = 0.006), and between PDGF-B expression and increasing proliferating cell nuclear antigen index (P = 0.01) was found. All tumors were also demonstrated to express the beta receptor of PDGF via immunohistochemistry. These studies suggest that PDGF-B expression may be an important mediator of cell proliferation control, via an autocrine mechanism, in human soft tissue tumors and may correlate with clinical outcome in the sarcomas.