During generalized immune responses such as the acute phase of graft-vs.-host reaction (GvHR) or many systemic viral infections the macrophage-monocyte system of mice is activated as demonstrated by their increased bactericidal capacity against Listeria monocytogenes. To study the effect of interferon (IFN)-gamma in maintainance of macrophage activity, lymphocytic choriomeningitis virus (LCMV) primed C57BL/6 mice or (C57BL/10 x B10.BR) F1 mice undergoing a GvHR were treated with polyclonal specific sheep anti-IFN-gamma antiserum. In both cases injection of anti-IFN-gamma resulted in inhibition of the stimulatory effects on macrophages as detected by reduced bactericidal activity when compared to mice treated with normal serum. Treatment with a polyclonal sheep anti-IFN-alpha,beta antiserum on the other hand did not interfere with the activation status of the macrophages. The findings suggest that IFN-gamma is produced both early in a GvHR and during the acute phase of an systemic infection with LCMV, and that it is involved in in vivo modulation of the increased activity of mononuclear phagocytes in immunologically stimulated mice.