Fibroblasts of the periodontium may be involved in extracellular matrix degradation in response to inflammatory cytokines produced by mononuclear phagocytes. Interleukin 1 (IL1), one of these biologically-active agents, is produced by such cells when stimulated by lipopolysaccharide (LPS). Periodontal-ligament (PLF) and gingival fibroblasts responded to recombinant human IL1 beta and to media conditioned by LPS-stimulated mononuclear phagocytes by secreting prostaglandin E (PGE). This response was dose- and time-dependent. Stimulated gingival fibroblasts also produced about five- to ten-fold as much collagenolytic activity when compared to controls but PLF produced no more activity. On mixing the conditioned media from both fibroblast types, inhibitory activity was found in the PLF-culture medium. Thus gingival fibroblasts in particular may be involved in the pathogenesis of periodontal disease by responding to factors produced by inflammatory phagocytes.