A new test principle for the simultaneous detection of total approximate titers and immunoglobulin M antibodies has been developed and applied to the detection of antibody to hepatitis B core antigen. The method is based on the combination of a competition radioimmunoassay, for the determination of total antibody titer, with an indirect enzyme-linked immunosorbent assay for the determination of single class antibodies. The interference of the rheumatoid factor was avoided by including heat-aggregated immunoglobulin G in the dilution buffer. The specificity, sensitivity, and clinical application of the test are discussed. The results presented suggest that the simultaneous detection of total and immunoglobulin M antibody to hepatitis B core antigen might be helpful in the differentiation between previous and recent or ongoing hepatitis B infection, as well as in the differential diagnosis of acute hepatitis, in monitoring viral activity in chronic infections, and in helping to differentiate acute from chronic infections. The test principle appears applicable in the accurate diagnosis of other infectious diseases by a single test on only one serum sample.