Chronic periodontitis affects many adults in the United States, some severely enough to threaten tooth loss. Of particular clinical importance is whether scaling and root planing (SRP) accompanied by a local adjunctive therapeutic agent improves outcomes over time compared to SRP alone. The adjunctive therapeutic agents investigated include: tetracycline, minocycline, metronidazole, a group of other antibiotics, chlorhexidine, and a group of antimicrobials. Primary outcomes considered are reductions in probing depth (PD) and gains in clinical attachment level (CAL). Methods: RTI-UNC Evidence-Based Practice Center staff searched MEDLINE (1966 through December 2002) and EMBASE (through February 2002) to identify clinical trials published in English that 1) involved adults with chronic periodontitis but no serious comorbidities; 2) tested one or more chemical antimicrobial agents as an adjunct to SRP alone or with a placebo; 3) had a concurrent control group that received the same SRP as the treatment group; 4) reported outcomes for specified, fixed time periods; and 5) if multiple antimicrobials were tested, reported outcomes for each agent separately. We performed qualitative analyses and meta-analyses of PD and CAL effect sizes when the necessary data were available from at least three studies at 6-month follow-up. Results: Among the locally administered adjunctive antimicrobials, the most positive results occurred for tetracycline, minocycline, metronidazole, and chlorhexidine. Adjunctive local therapy generally reduced PD levels. Differences between treatment and SRP-only groups in the baseline-to-follow-up period typically favored treatment groups but usually only modestly (e.g., from about 0.1 mm to nearly 0.5 mm) even when the differences were statistically significant. Effects for CAL gains were smaller and statistical significance less common. The marginal improvements in PD and CAL were a fraction of the improvement from SRP alone. Conclusions: Whether such improvements, even if statistically signi- ficant, are clinically meaningful remains a question. A substantial agenda of future research to address this and other issues (e.g., costs, patientoriented outcomes) is suggested.