Chronically inflamed tissues and most malignancies have antigenic properties. Patients with long-standing inflammatory bowel disease (IBD) are prone to development of colorectal cancer, which is known to shed antigens in the bloodstream. In an effort to study immunological aspects of these diseases, sera from patients with IBD and colorectal cancer were evaluated for presence of circulating antigen-antibody immune complexes (CIC), and compared to normal controls. CIC were precipitated by polyethylene glycol (PEG) and found to be elevated in all diseased groups. Dissociation of CIC and quantification of their antibody component revealed significant elevation of each immunoglobulin in IBD and in patients with colorectal cancer versus control: IgG = 1.776 +/- 1.573 vs 0.734 +/- 0.618 (P less than 0.001); IgA = 0.368 +/- 0.452 vs 0.090 +/- 0.198 (P less than 0.001); IgM = 0.434 +/- 0.235 vs 0.080 +/- 0.285 (P less than 0.001) serum total Ig levels were consistently much higher than CIC Ig. No correlation was found between the individual serum Ig components and the precipitable complexes-bound Ig, suggesting a selective recognition of antigenic components in the CIC, rather than non-specific association and subsequent precipitation of serum Ig. CIC may represent an easily accessible source of immunological determinants for the study of malignant and chronic inflammatory diseases.