The aims of the present study were to evaluate the clinical efficacy of, and to monitor microbiologically, repeated oral hygiene instructions alone or in combination with metronidazole 25% gel or subgingival scaling with or without metronidazole gel in treatment of new, residual or recurrent periodontal pockets in previously treated adult periodontitis patients. Ten suitable patients were included in this randomized single-blind clinical study with an intra-individual design. Clinical parameters were measured before and at 1, 3, 6, 9 and 12 months after treatment. Subgingival plaque samples were taken at every examination from one selected site in each quadrant. Smears from plaque samples were silver-stained and differential counting was performed under light microscopy at 1000X magnification. Four treatment modalities: (i) oral hygiene instruction (OHI) alone; (ii) OHI and metronidazole dental gel; (iii) OHI and subgingival scaling; (iv) OHI and subgingival scaling plus metronidazole gel, were randomly assigned to one quadrant of each patient. At the 12-month examination, the mean reductions in probing pocket depth were 2.6 mm after OHI alone, 2.8 mm after OHI and metronidazole gel, 3.3 mm after OHI and subgingival scaling and 2.6 mm after oral OHI and subgingival scaling plus metronidazole gel. The mean gains in probing attachment level were 2.2 mm, 1.9 mm, 2.7 mm and 1.6 mm, respectively. Although there were statistically significant differences in treatment responses between some treatment modalities at some time points, these were not considered to be clinically significant. Differential counts showed a shift towards a healthy microflora in response to all treatment modalities. From the 12-month results, it was concluded that the metronidazole 25% gel produced positive effects on the clinical parameters and on the subgingival plaque microbiological composition in new, residual or recurrent pockets in previously treated chronic periodontitis patients. However, the metronidazole gel alone or in combination with scaling does not seem to have any additional clinically significant therapeutic effects over and above those derived from improved oral hygiene resulting from monthly recalls, with or without subgingival scaling.