Irradiated peripheral blood lymphocytes from patients with chronic B-lymphocytic leukemia (B-CLL) have been shown to secrete a factor or factors that caused inhibition of malignant cell proliferation. In the present study, we used the murine B cell leukemia (BCL1) model system to examine the possible secretion of inhibitory factors from irradiated leukemic spleen cells. It was found that under culture conditions, irradiated spleen cells obtained from leukemic mice produce factors capable of suppressing BCL1 cell proliferation in vitro. The release of an inhibitory factor from nonirradiated cells was also observed, albeit to a lower extent. Supernatants collected from cultured nonirradiated and irradiated cells derived from animals at the first week after BCL1 cell inoculation did not affect the proliferation capacity of cells at any stage of the disease, whereas supernatants obtained at more advanced stages exhibited an inhibitory effect on the proliferation of cells derived from the same stages. The suppressive effect of supernatants of irradiated cells was more pronounced when those of 7 days' culture were used, compared to those of nonirradiated cells. The difference in suppression observed between supernatants of irradiated and nonirradiated BCL1 cells may be attributed either to the same factor produced in a larger amount following irradiation or to two (or more) factors--one produced spontaneously, the other induced by irradiation.