We investigated the relationship between the sensitivity of mouse splenocytes in immune response to nitrogen oxides and energy consumption rate of the cells. Macrophage-like cells (Mm1) pretreated with IL-6 served as the source of the nitrogen oxides. The antibody production of both 2,4,6-trinitrophenyl-keyhole limpet haemocyanin-primed splenocytes and B cell hybridomas was markedly reduced; about 20-40% of splenocytes and B cell hybridomas were killed by co-culture with IL-6-treated Mm1. Cell viability and antibody production were completely restored by the addition of NG-monomethyl L-arginine to the culture medium. The cytotoxicity of the nitrogen oxides was correlated with the distance between effector and target cells. Under conditions of low cytotoxicity, antibody production by B cell hybridomas was suppressed by the nitrogen oxides, this suppression not being correlated with the reduction in cell growth. The sensitivity of the target cells differed in co-cultures of antigen-primed splenocytes and B cell hybridomas with IL-6-treated Mm1. The nitric oxide-sensitivity of the cells corresponded to their 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reducing activity and ATP consumption rate. These findings suggest that nitrogen oxides act as regulatory molecules in immune response in three ways: cytostasis, reduction of cell growth and suppression of antibody synthesis.