By using three different assay methods, circulating immune complexes have been detected in 85% of sera from patients with malignant melanoma, and in 77% of sera from patients with breast cancer. These methods were a C1q-binding assay, a double-antibody conglutinin-binding ELISA, and a polyethylene glycol 6000 precipitation technique followed by quantitative determination of immunoglobulins in the redissolved precipitate. Detection rates of circulating immune complexes using any one of these methods separately ranged from 33% to 56%, indicating the presence of different types of circulating immune complexes in cancer patients' sera. The combined use of the three methods mentioned resulted in an increased diagnostic sensitivity and a doubling of the predictive value. However, tests for circulating immune complexes cannot be considered as useful parameters for early diagnosis of cancer, since the comparatively low incidence of malignancies in the population at large, together with the presence of circulating immune complexes in other, nonmalignant, diseases of considerable prevalence, appears to preclude effective application of any nonspecific method for early diagnosis of cancer in general.