To examine whether tissue levels of interleukin 6 (IL-6) are associated with the clinicopathologic status in human breast cancer, immunoreactive IL-6 concentration was measured in tumor extracts of 75 breast cancer patients. IL-6 was detectable in 69 of 75 tumor extracts by enzyme-linked immunosorbent assay, the concentration ranging from 10 to 10.690 pg/mg protein. When breast cancer specimens were categorized into four groups in terms of clinical stage of disease at diagnosis, IL-6 concentration (mean +/- SE) in tissue extracts was significantly higher in stage IV patients (2859 +/- 840 pg/mg protein) than in stage I-III patients (344 +/- 117, 350 +/- 150 and 564 +/- 230 pg/mg protein, respectively). Correlation analyses between IL-6 concentration and clinicopathologic factors showed that tissue levels of IL-6 were significantly higher in patients with distant metastasis compared with those without. Furthermore, IL-6 concentration was significantly higher in tumors of more than 5.0 cm in size as compared to less than 5.0 cm. However, no significant association was found between IL-6 concentration and age, histological type, histological grade, lymph node involvement, or hormone receptor status. These results suggest that primary tumor levels of IL-6 are closely associated with clinical stage in human breast cancer.