Two prophylactic immunosuppressive drugs, cyclosporine and methylprednisolone (MP), were compared for their effect on the in situ inflammatory reaction of granulation tissue formation and on wound healing. Granulation tissue was generated via implantation of viscous cellulose sponges in Sprague-Dawley rats. The rats were divided into 6 groups: 1 group received 40 mg/kg per day of cyclosporine, the second 10 mg/kg per day of cyclosporine, the third 2.5 mg/kg per day of cyclosporine, the fourth 12 mg/kg per day of MP, the 5th received the cyclosporine solvent, and the 6th group was given only saline. All drugs were given i.p. No reduction in the number of inflammatory cells was observed in the cyclosporine-treated sponges compared with the controls; MP suppressed the inflammation strongly. Differential counts demonstrated a relative enrichment of macrophages in the cyclosporine-treated vs. the MP-treated or control sponges. Chemical analyses of the sponge extracts agreed well with the cytological data: MP suppressed the total DNA content of the sponges, a marker of total cellularity, as well as the content of acid phosphatase and .beta.-glucuronidase, both markers of macrophages, but no such suppression was seen in the cyclosporine-treated sponges. The alkaline phosphatase content, a marker for granulocytes, was similar in all groups. A remarkable supppression in the contents of hydroxyproline, reflecting the amount of collagen and in that of Hb, reflecting the amount of neovascularization, was observed in the MP-treated sponges, whereas no such suppression, but possibly slight enhancement of the 2nd parameter, was observed in the cyclosporine-treated sponges. In contrast to MP, cyclosporine evidently does not inhibit the inflammatory reaction of granulation tissue formation or the regenerative process of wound healing.