The present study tested the hypothesis that treatment-resistant periodontitis patients present with a more intense inflammatory response to marginal bacterial plaque as a sign of an inflammatory overreaction. Patients with severe marginal periodontitis (Gingival Index > 20%) who had not responded to treatment showed almost no positive response to lipid A in a skin-prick test, which was significantly different from the results from patients with severe marginal periodontitis who had responded to treatment and from healthy control individuals without marginal periodontitis. This finding can be interpreted as an impaired inflammatory reactivity to periodontitis pathogens in treatment-resistant patients, rejecting the hypothesis.