An immunodiffusion system detecting an antigen showing immunological identity with international laboratory reference sera was developed by use of acute-phase and recovery sera from patients with transmission-proven non-A, non-B acute hepatitis. In other liver diseases the antigen was also present in a high proportion of patients and there were similar findings in conditions with high levels of circulating immune complexes in the serum. Fractionation of antigen-containing sera by column chromatography, polyethylene glycol treatment, and reduction and alkylation also suggested that immune complexes may be responsible for antigenic activity. The precipitation lines did not develop in the presence of 10 mmol/l EDTA or at a pH less than 8.0 and the reactant in "antibody" containing sera was shown not to be an immunoglobulin. Although the transmission of non-A, non-B hepatitis by blood and blood products shows that viral antigens are likely to be present in the circulation, this study shows that immune reactions apparently closely associated with the infection may be detecting immune complexes rather than specific viral components and emphasises the need for careful evaluation of the specificity of other reported serological tests for non-A, non-B hepatitis.

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