Although the chemotaxis and efflux of functionally normal polymorphonuclear leukocytes (PMN) into the periodontal sulcus may have a protective role in periodontitis, these cells are also associated with periodontal tissue destruction. The immunomodulating agent, levamisole hydrochloride, is known to enhance PMN chemotaxis. The present study was designed to evaluate the effects of enhanced PMN chemotaxis on the tissue destruction associated with an experimental periodontitis. Levamisole was administered by oro-gastric intubation to 4 squirrel monkeys (experimental) at 3 mg/kg/bw every 2 days for 18 days. After 2 doses of levamisole, marginal periodontitis was induced around maxillary and mandibular bicuspids and the maxillary first molars by tying plaque-retentive ligatures at the gingival margins. Periodontitis was induced around corresponding teeth in 4 animals (control) which had not received levamisole. All animals were killed 2 weeks after induction of periodontitis. Clinically, gingival inflammation was more pronounced in experimental animals at both 7 and 14 days after periodontitis induction. The progression of periodontitis was evaluated histometrically and alterations in the cell populations characterized using step serial sections. The results were analyzed statistically. No significant differences were observed between the groups with respect to areas of infiltrated supracrestal connective tissue and total numbers of cells present, loss of connective tissue attachment and loss of coronal alveolar bone. However, in experimental specimens, a much denser band of inflammatory cells was evident between the apical extent of the bacterial plaque and the gingival sulcular tissues the connective tissue of which contained significantly fewer inflammatory cells and demonstrated more pronounced fibrogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)