Rheumatoid factors (RF) were associated with alterations of antibody reactions to melanoma cells in vitro by two serologic assays. Removal of RF from melanoma patients' sera by absorption with Cohn's Fraction II coated latex particles enhanced seroreactivity in the Immune Adherence (IA) assay and diminished IgM detection by the Indirect Membrane Immunofluorescence (IMI) assay. The addition of serum with high titers of RF to these assay systems led to diminution of IA reactivity and enhancement of IgM detection by IMI. Since these factors are found in cancer patients' sera and can alter humoral immune reactions directed against antigens on the membranes of tumor cells, their presence should be recognized when performing assays with tumor target cells. RF may be of significance in the host-tumor relationship in vivo.