Background: Hyaluronan plays an important role in embryonal development, inflammation, wound healing, angiogenesis, and tumorigenesis. Although the activation or inhibition of matrix metalloproteinases (MMPs) has also been observed in such conditions, the relationship between hyaluronan and MMP activity is not fully investigated. Therefore, the effects of hyaluronan on MMP activity were examined in human skin fibroblasts. Methods: Quiescent subconfluent cells were cultured for 2 days in the presence of hyaluronan of differing molecular weights. The conditioned media were treated with Streptomyces hyaluronidase. The fractions precipitated with 80% saturation of ammonium sulfate were collected from the media and used as enzyme preparations. MMP activity was examined using gelatin or casein zymography. Results: Gelatin zymography showed an increase of MMP-2 (gelatinase A) activity, especially by higher-molecular weight hyaluronan preparations (800 and 1200 k). MMP activity appearing as a 47-kDa band was also increased in the same way. In contrast, casein zymography showed a decrease of MMP-3 (stromelysin-1) activity in the presence of hyaluronan, regardless of its molecular weight. Conclusions: These results suggest that hyaluronan has some effect on MMP activity and may be linked to proteolytic tissue remodeling in various physiological and pathological conditions.