Proteoglycans (PG) are altered in the asthmatic airway wall. As PGs are known to affect cell proliferation and apoptosis, we hypothesized that alterations in PG might influence the airway smooth muscle (ASM) hyperplasia observed in the asthmatic airway. Human ASM cells were seeded on plastic, or plates coated with decorin (Dcn), biglycan (Bgn) or collagen type I (Col I) (1; 3 and 10 µg/ml). Cells were stimulated with platelet-derived growth factor and cell number assessed at 0; 48 and 96 h. Cell proliferation was measured by BrdU incorporation, and apoptosis by Annexin V and propidium iodide staining, at 48 h post PDGF stimulation. A significant decrease in cell number was observed with cells seeded on Dcn (10 µg/ml) at 0, 48 and 96 h (p<0.01). Dcn induced both decreases in BrdU incorporation and increases in Annexin V staining (p<0.05). Bgn decreased cell number at time 0 only (p<0.05) and affected neither proliferation nor apoptosis. Col I (10 µg/ml) caused a significant increase in cell number at 48 and 96 h (p<0.01). Adding exogenous Dcn (1-30 µg/ml) to the medium had no effect on cell number. Exposing Dcn-coated matrices to chondroitinase ABC, an enzyme that degrades glycosaminoglycan sidechains, reversed the Dcn-induced decrease in cell number. These studies demonstrate that different PGs have variable effects on ASM cell proliferation and apoptosis. Recently described decreases in Dcn in the asthmatic airway wall could potentially permit more exuberant ASM growth.