This study assessed the effect of periodontal therapy on specific serum antibody concentration, expressed as titer, and antibody binding strength, expressed as relative avidity. The immune responses to Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans were investigated. Antibody titer was assayed by enzyme-linked immunosorbent assay (ELISA) and relative avidity was measured by thiocyanate elution in 17 adult periodontitis patients before and after therapy. Immunoglobulin G (IgG) avidities (expressed as thiocyanate molarity) to P. gingivalis increased from 1.01 to 1.38 M (P = 0.05) and IgA titers (expressed as ELISA units [EU]) increased from 89 to 237 EU (P = 0.012). There were no significant changes in avidity to A. actinomycetemcomitans, but the titer of all three immunoglobulin classes increased significantly (P < 0.03). More specifically, when patients were divided into subgroups which had originally been either IgG seropositive (i.e., having an IgG titer to this organism > 2 times the control median) or seronegative for P. gingivalis, only patients who were initially seropositive showed a significant increase in antibody avidity (P = 0.026; mean difference, 0.69 M). Patients who were originally seropositive in terms of IgG and IgA titer to P. gingivalis had demonstrably better treatment outcomes in terms of a reduced number of deep pockets and sites which bled on probing (P < 0.05). These findings suggest that periodontal therapy affects the magnitude and quality of the humoral immune response to suspected periodontopathogens, that this effect is dependent on initial serostatus, and that initial serostatus may have a bearing on treatment outcome.