The clinical and microbial effects of a single episode of simultaneous ultrasonic scaling and subgingival irrigation with chlorhexidine (CHX) were studied as a function of clinical probing depth in patients with adult periodontitis. 60 patients were randomly assigned to receive subgingival irrigation under cavitation with either sterile water or 0.12% CHX delivered through the tip of an ultrasonically activated scaler as part of initial periodontal therapy in a double-blind study design. 3 periodontal sites were randomly selected for examination from each patient on the basis of clinical probing depth, with 1 site being selected within each of the following ranges: 1-3 mm, 4-6 mm, and 7-9 mm. Pretreatment and post-treatment (days 14 and 28) clinical assessments included a plaque index (PI), gingival index (GI), and clinical probing depth (CPD). Subgingival specimens also were collected from 1-3 mm and 4-6 mm sites on a random subset of patients (15 per group). Plaque counts of spirochetes and motile organisms were made by darkfield microscopy. Significant reductions in PI, GI, and CPD were observed among all sites within both treatment groups at 14 and 28 days post-treatment. CHX irrigation resulted in a significantly greater reduction in CPD than did water among sites initially probing 4-6 mm at both 14 and 28 days post-treatment (25% versus 13% and 31% versus 18%, respectively). Spirochete counts were modestly but nonsignificantly reduced at 14 days post-treatment among sites 4-6 mm within both treatment groups. These results suggest that subgingival irrigation with CHX during ultrasonic scaling provides differential clinical benefits that are site-dependent.