In peripheral tissue, IL-1β has been shown to induce TNFα expression and vice versa, resulting in mixed neutrophil and mononuclear cell recruitment to the site of injury. This has led to the concept of crosstalk in peripheral cytokine signalling pathways. In the brain parenchyma, however, restricted patterns of leukocyte recruitment following the focal injection of pro-inflammatory agents into the brain are observed. This study investigates the expression of the principal pro_inflammatory cytokines—IL-1β and TNFα—in the brain after IL-1β, TNFα, NMDA or endotoxin injection into the brain parenchyma of rats. Each of these agents gives rise to a distinct pattern of acute leukocyte recruitment at 24 h. We found that IL-1β induces de novo synthesis of additional IL-1β but not TNFα, as determined by RT-PCR and ELISA, and TNFα does not induce either itself or IL-1β. Injection of NMDA results in IL-1β, but not TNFα up-regulation. Injection of IL-1β or NMDA is associated with neutrophil recruitment whereas injection of TNFα is associated with mononuclear cell recruitment. Following injection of endotoxin, both TNFα and IL-1β levels are elevated and neutrophils and mononuclear cells are recruited to the brain. These data suggest that the signalling pathways that are present in the periphery are modified in the brain and that differential induction of TNFα and IL-1β may have a role in the atypical pattern of leukocyte recruitment observed in the brain.