A study was undertaken to assay and compare the pathological potential of loosely adherent plaque (LAP) with that of adherent plaque (AP) using the limulus lysate assay (LLA). A technique was devised for collection both AP And LAP from supra‐ as well as subgingival tooth areas under pyrogen‐free conditions. Five supragingival samples (AP&LAP) were collected from teeth (G.I.=<1) after subjects had abstained from tooth cleaning for two weeks. Five subgingival samples were collected from mylar strips one week after placement in periodontal pockets not less than 4 mm and not more than 7 mm in depth. All samples were lyophilized, recontituted and analyzed for plaque mass by the quantitative ninhydrin reaction (Moore and Stein, 1954). Samples were analyzed for limulus lysate activity by a modification of the LLA of Levin and Bang (1964).Results from the five supragingival samples indicate that plaque mass, as determined by the ninhydrin reaction, was 4–5 fold greater in AP than in LAP. In the five subgingival samples, ninhydrin values for AP were two times higher than LAP. In spite of these differences in plaque mass, limulus activity in all LAP samples was consistently higher than in comparable AP samples when expressed as limulus activity per mole of amino acid. These preliminary findings suggest that subgingival LAP, situated in a position of strategic importance, is biologically active and deserves further