The effects of human interleukin 1β (IL-1β) and prostaglandin E ₂ (PGE ₂) on experimental granulation tissue in rats and on granulation tissue cells in culture were studied. IL-1β and PGE₂ were injected into subcutaneously implanted sponges during the first 3 days after implantation. The rate of collagen synthesis in fibroblasts was measured as synthesis of protein-bound ³ H-hydroxyproline. The steady-state levels of proα1(I) and proα1(III) collagen chain mRNAs were estimated by Northern transfer analyses. By 7 days postoperatively IL-1β had decreased the hydroxyproline content of granulation tissue. PGE ₂ decreased nonsignificantly the amounts of hydroxyproline, but the steady-state levels of proα1(I) and proα1(III) collagen chain mRNAs were slightly elevated. In IL-1β-treated fibroblast cultures collagen production decreased by 15% and following PGE ₂ treatment by 34% compared with the controls. The latter effect could be abolished by indomethacin. Indomethacin alone stimulated collagen production by 40%. In vivo IL-1 decreases the formation of normal granulation tissue. This effect may be partly due to stimulation of secretion of PGE ₂.