Natural cytotoxicity was studied before surgery or other treatment in 83 women with primary, untreated breast cancer. Peripheral blood lymphocytes (PBL) and cytotoxicity of regional lymph node cell(s) (RLNC) were examined in a 4-hour 51Cr release assay against the target cell K-562. Results indicated that greater than one-third of breast cancer patients have more negative lymphocyte cytotoxic activity toward K-562 than do the other two-thirds. Similar results were observed for PBL of 25 patients found to have benign breast lesions. Of these patients, 23 had fibrocystic disease. The difference between these findings and findings with normal control lymphocytes studied in parallel was highly significant (P less than 0.001). The study of RLNC cytotoxicity in patients with breast cancer showed that 25% of the patients' RLNC had significant natural cytotoxic activity toward K-562. Incubation of RLNC with interferon in vitro before addition of labeled K-562 cells did not induce cytotoxicity in RLNC that did not have this activity initially.