The current study compared the clinical, microbiological and immunological parameters of chronic periodontitis patients that received two different treatment strategies: one-day full-mouth scaling and root planing (FM-SRP) versus quadrant scaling and root planing at two-weekly intervals (Q-SRP). In addition, the effects of smoking on the periodontal status, subgingival microflora and humoral immune response were examined. Clinical measurements, subgingival plaque samples, gingival crevicular fluid (GCF) and sera were collected from 42 patients with moderate to advanced chronic periodontitis before and after treatment over a period of six months. Patients were randomly allocated into two treatment groups and received FM-SRP or Q-SRP. Polymerase chain reaction (PCR) was used to determine the presence of P. gingivalis, A. actinomycetemcomitans, P. intermedia, T denticola and B. forsythus in plaque. Enzyme-linked immunosorbent assay (ELISA) was used to examine systemic and local antibody titres to these bacteria and thiocyanate disassociation was used to determine antibody avidity. Q-SRP and FM-SRP were found to be equally efficacious periodontal treatments. Therefore, the clinician should decide which treatment strategy to choose on a practical basis. No evidence emerged from this study to document a strong immunological reaction elicited by FM-SRP, as was speculated by Quirynen et al. (1995). In fact, during therapy the host responses of patients in both treatment groups followed a similar pattern. In general, both treatments resulted in significant clinical improvement and reduced titres of antibodies, but which were of similar avidity for the majority of the tested organisms. These changes paralleled marked reductions in the site and subject prevalence of putative periodontopathogens. In addition the present data do not support the hypothesis that, during the active phase of quadrant root planing therapy, the treated sites are re-infected with organisms that are possibly transmitted from the remaining untreated pockets and from other intra-oral niches (Quirynen et al. 1995). In contrast, the commencement of quadrant root planing and meticulous oral hygiene measures had a significant positive effect on the periodontal conditions of the remaining untreated quadrants. Nevertheless, this clinical improvement was smaller compared to changes seen after the completion of mechanical debridement. Despite the fact that FM-SRP resulted in significantly higher pain scores and more patients taking analgesics compared to Q-SRP, it still seemed to be well tolerated by patients. Smoking had a significant adverse effect on the inflammatory response to the bacterial challenge and on the treatment outcome. The outcome of each treatment strategy (Q-SRP and FM-SRP) was affected significantly by smoking over the course of treatment, having a significant impact on pocket depth (PD) and relative attachment level (RAL) of selected sites. A smaller PD reduction and less gain in RAL were noted after both treatment strategies at selected sites of smokers compared with those of non-smokers. Smoking appeared to modify both local and systemic host responses by producing lower levels of GCF and serum antibodies, respectively, but appeared to have no significant effect on the subgingival microflora. This study associated systemic antibody levels with the presence of homologous organisms in subgingival plaque. Furthermore, the present study showed that subjects with less severe disease and a better clinical outcome retained higher levels of serum antibodies compared to patients who had more advanced disease and a moderate clinical outcome. These findings confirm the suggestions from other studies that antibodies are protective against the progression of periodontal disease. GCF antibody titres were low compared to serum antibody levels, which agrees with previous findings and a large site-to-site variability was evident, making interpretation of the results difficult. Nevertheless, it was apparent that deep pockets and sites that harboured a bacterial species gave rise to higher levels of GCF antibodies for that species