Previous studies have indicated that S-adenosylmethionine (SAMe), the precursor of methyl groups and thiols, exerts an anti-inflammatory activity. In order to clarify whether this molecule also has antifibrotic properties, we evaluated its pharmacological effects on human fibroblasts in vitro. Accordingly, fibroblasts between 5 and 10 subcultures were incubated for 24 h with different SAMe concentrations (from 0.005 to 626 microM). Fibroblast proliferation measured by incorporation of labeled thymidine was not affected by SAMe in the range of the tested concentrations. Moreover, cell viability assessed by trypan-blue exclusion test was greater than 98% in all cultures, without any difference between SAMe and control cultures. Collagen synthesis estimated by HPLC measurement of hydroxyproline in both media and cells was not modified by SAMe concentrations lower than 0.05 microM. On the other hand, SAMe concentrations higher than 0.05 microM significantly (p less than 0.01) reduced collagen synthesis as compared with untreated controls. This effect was not dose-dependent. In conclusion, this study indicates that SAMe addition to fibroblasts in the range of concentrations which can be found in vivo induces a marked decrease (about 50% of control value) in collagen synthesis with no adverse effects on cell proliferation and viability. These findings suggest further investigation of the potential antifibrotic role of SAMe.