Smoking is considered a risk factor for periodontitis and an impediment to treatment. The current studies evaluated the efficacy of the local administration of 1 mg minocycline hydrochloride encapsulated in a bioresorbable polymer in periodontal pockets of > or = 5 mm in all three studies. Two hundred and seventy one patients who smoked were enrolled in the two single blind controlled studies (data pooled) with efficacy compared to scaling and root planing (SRP) and 71 smokers were enrolled in an open label study. In the three studies SRP was performed at baseline and the unit dose minocycline administered at baseline, three and six months. Efficacy and safety were measured at one, three, six, and nine months. Adjunctive treatment resulted in statistically significant pocket depth reduction in both studies in these smokers. In the controlled studies the difference in probing depth reduction between the adjunctive therapy group and the SRP alone group was statistically significant at one, three, six, and nine months. No serious adverse events were recorded in any of the studies.