Lymphocytosis promoting factor (LPF) is a protein toxin which may have a role in the pathogenesis of pertussis. Previous results from our laboratory demonstrated that LPF inhibited random migration and chemotaxis of resident peritoneal macrophages, but had little or no effect on macrophage viability, adherence, superoxide anion release, or Fc-mediated phagocytosis. The current experiments have examined mononuclear phagocyte function in mice treated with LPF. Intravenous injection of mice with 200 ng LPF induced a prolonged monocytosis which peaked with a five-fold increase on the fifth day after injection. LPF (200 ng) also inhibited the increase in peritoneal macrophages induced by the intraperitoneal injection of either thioglycolate broth, phytohemagglutinin, or paraffin oil. The LPF-induced monocytosis on the fifth day after injections was not altered by the intraperitoneal injection of thioglycolate broth. LPF doses sufficient to induce leukocytosis (greater than or equal to 25 ng) significantly inhibited the increase in peritoneal macrophages induced by an inflammatory agent. These observed in vitro and in vivo effects of LPF were lost when LPF was subjected to treatments that eliminated its leukocytosis-promoting activity. The results indicate that coincident with an LPF-induced monocytosis is a reduction in the number of macrophages at a site of inflammation. An in vivo inhibition of mononuclear phagocyte migration would explain both of these effects of LPF, and is consistent with the in vitro inhibition of macrophage migration. The results suggest that a possible role for LPF in pathogenesis is the inhibition of macrophage migration to the site of Bordetella pertussis infection.