Sera from 8 patients with osteosarcoma and 64 normal individuals were examined by C1q and Raji cell radioimmunoassays for the presence of circulating immune complexes. Of the 8 patients with osteosarcoma, 6 had elevated levels of immune complexes in their sera. The elevated levels of immune complexes were demonstrated by both the C1q radioimmunoassay and the Raji cell radioimmunoassay. The amount of immune complexes was quantitated by Raji cell radioimmunoassay; the mean plus or minus the standard error of the amount of aggregated human IgG equivalent per milliliter of serum was 80.12+/-72.64 micrograms for patients with osteosarcoma and 23.07+/-6.2 micrograms for normal individuals. The blocking effect of sera from patients with osteosarcoma on lymphocyte cytotoxicity against cultured osteosarcoma cells (TE-85) was examined. The result indicated that sera with elevated amounts of immune complexes also had increased levels of blocking activity. Sera were fractionated to separate immune complexes from gamma-globulins. No free tumor-specific antibody could be detected in fractionated gamma-globulin fractions from 2 patients with osteosarcoma. The sera of these patients had high amounts of immune complexes and high blocking activities.