The aim of this study was to determine whether same-day full-mouth scaling and root planing (FM-SRP) and quadrant scaling and root planing (Q-SRP) resulted in variations in the systemic humoral immune response dynamics (antibody titres and avidity) during active treatment and 3 and 6 months post-therapy. Material and Methods: Forty patients with chronic periodontitis were recruited into this study. Subjects were randomised into two groups and received either scaling and root planing quadrant by quadrant at 2-weekly intervals (Q-SRP group) or same-day full-mouth scaling and root planing (FM-SRP group). Clinical measurements and serum samples were obtained at baseline and approximately 6 weeks after the last clinical intervention (R1) and 6 months after the initiation of therapy (R2). Furthermore, serum samples were obtained from each patient undergoing therapy (Q-SRP and FM-SRP) at 3 bi-weekly instances so as to determine the short-term effects of each session of scaling and root planing on the dynamics of the humoral immune response. Serum antibody titre was assayed by enzyme-linked immunosorbent assay (ELISA) and antibody avidity was measured by thiocyanate dissociation against five putative periodontal pathogens: Porphyromonas gingivalis; Actinobacillus actinomycetemcomitans; Prevotella intermedia; Treponema denticola and Bacteroides forsythus. Results: Both therapies resulted in similar antibody titre reductions against the majority of the organisms tested and although there was a distinct trend for antibody avidity to increase following therapy, this was not found to be statistically significant, reflecting marked inter-individual variation. In addition, no evidence emerged from this study to support increased antibody titres following the active phases of both treatment approaches due to an inoculation effect. Nevertheless, significant short-term increases in antibody avidity to most test bacteria were noted for both treatment strategies. Conclusion: Both therapies were associated with a reduction in antibody titres and an increase in the binding ability or avidity of antibodies, but there was a marked inter-subject variability and statistical significance was reached for only some of the test bacteria. No significant differences in the humoral antibody dynamics were found between the two treatment approaches.