28 patients, 13 smokers and 15 non-smokers with untreated advanced periodontal disease, were subjected to a series of oral hygiene instructions and treated with non-surgical periodontal therapy. Baseline values regarding clinical data did not differ significantly between the groups. 6 months following therapy the full-mouth bleeding score among smokers was 36.5% as compared to 22.7% for non-smokers (p < 0.05). Probing depth was reduced by 1.9 mm for smokers and by 2.5 mm for non-smokers. This difference was statistically significant (p < 0.05). The level of P. gingivalis and P. intermedia/nigrescens was reduced in both groups as compared to baseline. A. actinonmycetemcomitans, however demonstrated a slight increase in mean values at 6 months. This was especially notable for smokers in which A. actinomycetemcomitans were more difficult to eradicate. Conclusively, the microbiological response found in this study seems to be in conformity with the clinical response with little influence of the smoking habits.