The direct leukocyte migration inhibition test was used to measure the host response to antigen preparations of autologous and homologous breast cancer and normal breast tissue, a panel of cancerous and normal colon tissue, and 3 breast cancer cell lines: MCF-7, CAMA and MD-MBA-231. A total of 96 patients with primary operable breast cancer, 22 patients with benign breast disease, 10 patients with head and neck cancer, and 40 normal women were tested. The migration index (MI) equivalent to the 10th percentile of the control response to individual antigens was used as the cutoff point determining the level of positive response. Only 19% of 62 patients responded to cryostat sections of autologous cancer vs. a 9% response to autologous normal breast tissue (P = not significant). Similar responses were observed with the use of saline extracts of these tissues. Positive response (MI < 0.93) to a panel of cryostat sections of homologous breast cancer antigens occurred in 44% of 96 patients with breast cancer, 15% of 39 patients with benign breast disease, and 12% of 140 normal women (P < 0.01). A similar pattern of response was observed with the use of saline extracts of these tissues, but none of the patients responded to saline extracts of normal or malignant colon tissue. The response to the MCF-7 breast cancer cell line was also significantly higher in the patients with breast cancer (50%) than in normal persons (9%) or in patients with head and neck cancer (10%, P < 0.01) but was not significantly higher than responses in patients with benign breast disease (24%, P < 0.1). The breast cancer patients showed variable response to 2 other breast cancer cell lines, CAMA (23% positive) and MD-MBA-231 (15% positive), which may indicate quantitative or qualitative differences in antigenicity between these breast cancer cell lines. The leukocyte migration inhibition response rates to homologous breast cancer antigens suggest possible previous sensitization to these antigens in a portion of the breast cancer patients. Whether the antigenic determinants are common to many breast cancers or are also distinctive for individual cancers remains to be determined.