We have previously demonstrated that aspirated breast cyst fluids from women with benign breast disease contained a particulate component (BCF-PC) that reacted with antiserum to the murine mammary tumor virus (MuMTV). Since women with breast cancer contain antibodies and antigens reactive with MuMTV it was of interest to measure the immune response in breast cancer patients to the BCF-PC. Sera were obtained from breast cancer patients prior to surgery and 5 days postmastectomy, from women with benign breast disease and from healthy women. Analysis for antibody to the BCF-PC was by an enzyme-linked immunosorbent assay. IgA from premastectomy breast cancer patients was significantly more reactive with the BCF-PC than was IgA from women in the other categories ( P < 0.001). In contrast, IgG binding to the BCF-PC did not differ among the various groups. It was further demonstrated that the reactivity of IgA from any particular serum for the BCF-PC remained constant for different BCF-PC isolates. Other fractions of breast cyst fluids were unreactive with IgA from breast cancer patients. Determination of serum IgA levels in these women revealed that the mean IgA level was significantly higher in healthy women than in the other categories ( P < 0.001). Individual IgA levels and levels of IgA antibody to the BCF-PC were found to be not correlated in breast cancer patients. These results indicate that the production of a specific IgA antibody to the BCF-PC increases in sera of patients with breast cancer. Lastly, it was shown that preincubation of patients' sera with disrupted MuMTV, but not intact MuMTV, severely reduced subsequent IgA binding to the BCF-PC. The analysis of sera for IgA antibody to the BCF-PC may be of value for the detection of breast cancer or its recurrence.