Perigraft fluid from Staphylococcus epidermidis infected grafts in a mouse model significantly inhibits fibroblast proliferation (60-98% at 7 and 28 days), compared with perigraft fluid from sterile grafts. The fibroblast inhibitor was trypsin-heat resistant and dependent primarily upon the bacteria, not the host proinflammatory mediators or the vascular graft biomaterial. We tested the inhibitory properties of S. epidermidis strains RP62A (slime producer) and RP62NA (nonslime producer) and Staphylococcus aureus strain 502a, using an in vitro tritiated thymidine murine fibroblast (ATCC CCL-12) proliferation assay. Whole killed bacteria, disrupted bacteria (live and killed), bacterial supernatants, and purified cell wall products (peptidoglycan, teichoic acid, and lipoteichoic acid from disrupted bacteria) were studied. Significant fibroblast inhibition occurred for all three bacterial strains with disrupted bacteria (live or killed) and cell free bacteria derived supernatants. The fibroblast inhibitor from disrupted slime producing S. epidermidis was trypsin-heat resistant. The fibroblast inhibitor from disrupted S. aureus and supernatants for all three bacterial strains at 1 x 10(7) were trypsin-heat sensitive. Fibroblast inhibition was not dependent upon bacterial viability and not mediated by bacterial cell wall products. In conclusion, components of slime and nonslime producing S. epidermidis and S. aureus inhibit fibroblast proliferation.