Since IgG subclasses are common immunoglobulins associated with the periodontium and have different biological characteristics, these subclasses were measured in gingival crevicular fluid (GCF) from periodontally active (greater than or equal to 2 mm clinical attachment loss within three months of sample) versus clinically similar but stable or healthy sites. A sandwich enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies was performed to quantitate IgG subclass and albumin concentrations in serum and interproximal GCF samples from at least one each of the three disease categories from each of 20 periodontal maintenance patients. Although much variability existed among sites, mean IgG1 (p less than 0.05) and IgG4 (p less than 0.01) concentrations were higher in GCF from active periodontitis areas than stable sites, even though both had similar clinical characteristics. When IgG subclass concentrations were adjusted per mg albumin, both IgG1 and IgG4 levels in GCF from active sites were still significantly elevated over stable areas (p less than 0.05). Mean adjusted concentrations in GCF were generally greater than in serum, especially for IgG4 (active site GCF:serum = 24.2:1). GCF IgG4 concentrations may be useful as an indicator of the immunopathological changes which occur in active periodontitis.