Cellular immune reaction plays an important role in tuberculous infection. When the host develops cellular immunity, a large number of activated macrophages (M phi) are accumulated in the tuberculous focus by the chemotactic effect of lymphokine, and these M phi lively phagocytize and suppress the multiplication of tubercle bacilli. On the other hand, many M phi are killed during the process of phagocytosis, releasing a large amount of lysosomal enzymes and cytotoxic substances (TNF etc.), possibly causing the tissue damage: caseous necrosis, softening and liquefaction followed by cavity formation. To clarify the process of necrosis in detail, production of TNF-alpha and IL-6 from human M phi was observed. Monocyte/M phi were separated from the peripheral blood of healthy persons, each group with positive or negative tuberculin reaction and tuberculous patients, using a commonly used method. The monocyte/M phi were stimulated in a culture with lipopolysaccharide (LPS) or muramyl dipeptide (MDP) and amount of TNF-alpha and IL-6 in the culture supernatants were estimated. TNF-alpha activity was determined by measuring the lysis of the target cell (mouse L929 cell), and IL-6 by measuring the 3H-thymidine incorporation into IL-6 dependent mouse plasma cell hybridoma, MH60-BSF2, in the presence of TNF-alpha or IL-6, respectively. The results showed that the monocyte/M phi from the tuberculin positive persons, with or without tuberculosis revealed a higher TNF-alpha production activity than those from tuberculin negative healthy cases using either MDP or LPS stimulation. The monocyte/M phi from tuberculous patients produced more TNF-alpha with MDP stimulation than with LPS.(ABSTRACT TRUNCATED AT 250 WORDS)