Transforming growth factor beta (TGF-beta) stimulated the synthesis of heparan sulfate proteoglycan in cultured human colon carcinoma cells without affecting its rates of intracellular degradation or secretion. The overall hydrodynamic size, electrophoretic mobility, and degree of sulfation of the TGF-beta-induced proteoglycan was indistinguishable from that of untreated cells. The synthesis of the protein core was significantly stimulated by TGF-beta, although total cellular protein was unaltered. The stimulatory effects of TGF-beta were prevented by the inhibitors of protein synthesis and DNA transcription, cycloheximide, or actinomycin D, respectively. Analysis of protein core mRNA levels using a murine cDNA encoding a basement membrane protein core, revealed a marked elevation of the steady state levels of mRNA for this gene product. In contrast, the mRNA levels for glyceraldehyde-3-phosphate dehydrogenase or beta-actin genes were not significantly affected by TGF-beta. Finally, nuclear run-off experiments showed increases in neither protein core-specific transcription nor in general transcriptional activity. Taken together, these results indicate that TGF-beta is a potent modulator of heparan sulfate proteoglycan expression in human colon carcinoma cells and that its effect is mediated primarily through an increase in mRNA levels encoding the protein core, perhaps a result of enhanced RNA stability. The TGF-beta-induced elevation of heparan sulfate proteoglycan may contribute to the control of stromal cell proliferation and matrix production by human colon carcinoma cells.