In order to simultaneously assessthe local humoral immune and polymorphonuclear leukocyte (PMN) responses in periodontal disease, IgG, IgM, and IgA, as well as the PMN lysosomal enzyme β‐glucuronidase (βG), were examined in gingival crevicular fluid (GCF) from patients with varying degrees of periodontal pathology. Evaluations were made before and after conservative therapy (scaling and root planing). Thirty patients with varying degrees of periodontal pathology, ranging from mild inflammatory gingivitis to moderate periodontitis, were studied. GCF was collected from the mesial surfaces of all teeth. The presence of the 3 Immunoglobulin isotypes was determined by enzyme linked immunosorbent assays (ELISA), while total βG activity in GCF was determined by a fluorometric assay. Clinical parameters were obtained from 6 sites per tooth. Our data indicate that prior to treatment, total βG activity is strongly related to the severity of periodontal disease as measured by mean probing attachment level (AL; r = 0.89;P<.005), mean probing depth (PD; r = 0.89;P<.0005) and percentage of sites exhibiting bleeding on probing (% BOP; r = 0.49;P<.005). Following treatment, no statistically significant relationship of disease severity and βG is found. The concentrations of IgG and IgM in GCF do not follow a specific pattern when related to disease severity. In contrast, prior to treatment the concentration of IgA is negatively correlated to mean AL (r = ‐0.54;P<.005), mean PD (r = ‐0.59;P<.005), and % BOP (r = ‐0.47,P<.005). Following treatment, the negative correlation of IgA concentration to the clinical parameters is not as strong as seen before treatment, but still reaches significance for AL and PD. We also examined individual sites within patients who were categorized as displaying either gingivitis or periodontitis. We compared sites of comparable probing depth (1 to 3 mm or 4 to 6 mm) in the two groups of patients. With these analyses, the inverse relationship of the concentration of IgA in GCF and clinical measures of periodontal disease is still observed, suggesting that this finding was independent of probing depth of the individual site, and is a characteristic of the patient. In summary, the increased concentration of IgA in GCF from patients with minimal periodontal pathology suggests that IgA may play a protective role in the crevicular environment. Furthermore, this investigation supports the concept that a biochemical profile of GCF can be used to investigate the nature of the host response in periodontal disease.J Periodontol 1995; 66:55–61.