Important constituents of extracellular matrix are collagen, fibronectin, hyaluronan, and various types of proteoglycans, such as versican, perlecan, decorin, and biglycan. Remodeling of extracellular matrix occurs continuously and is affected by various cytokines. The aim of this study was to investigate how interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α), separately and in combination, alter fibroblast proliferation, as well as the production of extracellular matrix molecules produced by human fibroblasts from lung. Fibroblast proliferation was inhibited significantly by all treatments, by 12% with IL‐1β and by 16% with TNF‐α. The combination of IL‐1β and TNF‐α increased the inhibition further, by 27%. Hyaluronan production was increased by all treatments: 1.7‐fold by IL‐1β and 1.5‐fold by TNF‐α. The combination of the two gave a further increase (2.5‐fold). Similarly, the production of total proteoglycans was increased. The small proteoglycans, decorin, and biglycan, were regulated differently. Decorin production was inhibited by about 34% by all treatments, while biglycan was upregulated 1.3‐fold by TNF‐α. Versican was upregulated by IL‐1β (1.7‐fold), whereas TNF‐α was without effect. Perlecan was mostly unaffected. The changes in protein production of the various proteoglycans were due to increased transcription, as mRNA levels were also changed to the same extent. Synthesis of mRNA for collagen type I was inhibited by up to 75% with the IL‐1β/TNF‐α combination. The separate cytokines also decreased the level of collagen type I mRNA, but to a lesser extent: 60% with IL‐1β and 40% with TNF‐α. In summary, our study indicates that these proinflammatory cytokines affect the regulation of extracellular matrix production, which is of importance for the inflammatory process. J. Cell. Biochem. 77:298–309, 2000. © 2000 Wiley‐Liss, Inc.