Fibrosis of subconjunctival tissues is a major cause of bleb failure following glaucoma filtration surgery. The aim of the present investigation was to demonstrate the effect of Rapamycin, a clinically relevant macrolide antibiotic with potent immunosuppressive properties, on human Tenon fibroblast proliferation induced by platelet-derived growth factor and basic fibroblast growth factor. Primary Tenon fibroblast cultures were derived from patients undergoing trabeculectomies or routine cataract extractions. Rapamycin was added in concentrations of 0.1-100 ng/ml with or without 3-30 ng/ml of porcine platelet-derived growth factor or of human recombinant basic fibroblast growth factor. Two days after treatment, the cells were examined and counted. The results were expressed as the percent of cell growth in treated culture relative to its untreated control. Rapamycin was not cytotoxic at any of the concentrations tested. Inhibition of platelet-derived growth factor-induced Tenon fibroblast proliferation occurred with all doses of Rapamycin, the most marked effect being observed with 30 ng/ml (60% inhibition, p < 0.001). In contrast, optimal inhibition of basic fibroblast growth factor-induced proliferation was only 37% (p < 0.01), achieved with 10 ng/ml of the peptide. Rapamycin potently inhibits platelet-derived growth factor-induced fibroblast proliferation in vitro without any apparent cytotoxicity. It may eventually prove to be a useful adjunct to glaucoma filtration surgery.