The aim of the present study was to compare stereologically the histopathologic variations following 3 weeks of chemical (chlorhexidine) or mechanical plaque control. 18 students and dental hygienists volunteered for this investigation. After prophylaxis, they performed optimal oral hygiene to reach mean plaque and gingival indices approaching 0. Six of them then performed mechanical plaque control of 3 weeks (control), while the other 12 rinsed 3 times daily with a 0.12% chlorhexidine solution (test). At days 0 and 21, the plaque index (PlI), the gingival index (Gl) and the gingival exudate flow rate (GEFR) were assessed and biopsies were obtained from buccal sites. Point-counting procedures were performed at 2 different levels of magnification on light microscopic sections to estimate the volume fractions of epithelium, infiltrated and non-infiltrated connective tissue, and collagen. The relative numbers of fibroblasts, polymorphonuclear neutrophils, lymphocytes, plasma cells, macrophages and mast cells were estimated by counting the number of nuclear profiles of these cells in a specific connective tissue area adjacent to the apical termination of the junctional epithelium. After 21 days, the PlIs of the test subjects were significantly higher than the PlIs of the controls, but their Gl were similar. At the end of the experimental period, the various volume fractions and %s of cell profiles remained stable with the exception of an increase in the %s of lymphocytes in the test group. This study has shown that, clinically as well as histologically, the daily use of chlorhexidine for a 3-week period is equally efficient as optimal mechanical tooth cleaning in maintaining a healthy gingiva in the buccal sites investigated.