OK-432, a streptococcal preparatopn, is a potent inducer of interferon-γ (IFN-γ) which is known to modulate the immune response. The OK-432-induced IFN-γ production of peripheral blood mononuclear cells (PBMC) was examined in 98 patients with malignant lymphoma, The PBMC were incubated in RPMI-1640 containing 0.1KE/ml OK-432 for 48 hours and the IFN-γ secreted in the supernatant was measured thereafter. Patients at diagnosis or those with relapsing disease showed a decreased production of IFN-γ compared with the healthy controls (P<0.001). The production at diagnosis was related to the clinical stage. The production was significantly decreased immediately after multi-drug chemotherapy. However, it recovered to the level of the healthy controls, once a patient achieved a complete response. At diagnosis, 13 of the 32 patients with non-Hodgkin's lymphoma showed low IFN-γ production. These patients responded poorly to chemotherapy or had early relapse. The 2-year actuarial survival rate was 54% for these patients and 92% for the remainder. There was no decrease in IFN-γ production after chemotherapy in patients treated with G-CSF. These findings suggest that measurement of OK-432-induced IFN-γ production is useful for evaluating the immunological status and predicting the prognosis in patients with malignant lymphoma. They also suggest that G-CSF affects the IFN-γ production in vivo.