Proteoglycans contribute to extracellular matrix remodeling in asthmatic airways. We investigated the effects of budesonide, a glucocorticoid, and formoterol, a long-acting ₂-adrenergic agonist, on serum-induced proteoglycan production by human lung fibroblasts. In 10% serum, total proteoglycan production was increased 1.5-fold (p<0.01) compared to basal production in 0.4% serum. Budesonide (10^-8 M) reduced this increase by 44% (p<0.01), and while formoterol (10^-10-10^-8 M) had no inhibitory effects, the drug combination abolished the increase (p<0.01) without affecting fibroblast proliferation. This synergistic effect required functional glucocorticoid and -adrenergic receptors. The production of the proteoglycans decorin, biglycan, perlecan, and versican, was increased 2.5-5-fold (p<0.01) in 10% serum. Combination treatment with budesonide (10^-8 M) and formoterol (10^-10 M) abolished this increase to a significantly greater extent than either drug alone. In 10% serum, only versican mRNA was increased 1.4-fold (p<0.05), while decorin mRNA was reduced to 39% (p<0.01) of basal expression. These serum effects were counteracted by the drug combination but without difference versus either drug alone. Thus, the budesonide and formoterol combination seems to synergistically control serum-induced proteoglycan production primarily at post-transcriptional level. In conclusion, the proteoglycan upregulation characteristic of asthmatic airways may be limited by combination therapy with budesonide and formoterol.