The production of nitric oxide (NO) by macrophages is important for the killing of intracellular pathogens, such as Toxoplasma gondii. Gamma interferon (IFN-gamma) and lipopolysaccharide stimulate NO production. The aim of this study was to investigate the importance of NO, IFN-gamma and interleukin-12 (IL-12) in the host immune response in AIDS patients suffering from toxoplasmic encephalitis (TE). It was demonstrated that the production of NO, detected as nitrite/nitrate in the sera and in the cerebrospinal fluid (CSF) of 32 AIDS patients with TE, was normal. In addition, levels of IFN-gamma in the sera and in the CSF of patients with TE were not increased. In contrast, serum levels of IL-12 in these patients were significantly increased (6.5 +/- 7.1 pg/ml; P = 0.0368), compared to the control patients (1.7 +/- 3.5 pg/ml). Furthermore, increased but not significant levels of IL-12 were also observed in the CSF of patients with TE (2.2 +/- 4.7 pg/ml; controls: 0.5 +/- 1.9 pg/ml). The results of this study indicate that reactivation or recurrence of T. gondii infection in HIV-1-infected patients is probably due to a down-regulation of IFN-gamma along with a resulting non-optimal NO activity.