Cellular responses to lipopolysaccharide (LPS) are enhanced by LPS-binding protein (LBP). The present study investigated the acute phase response of LBP during Trypanosoma brucei brucei infection in mice. Mean plasma concentrations of LBP increased two-fold by the seventh day following infection, but decreased to intermediate levels by the 14th day. There were no significant differences in LBP concentrations of infected/antibiotic-treated and infected/untreated mice. At 35 days post-infection, the infected mice were treated with the anti-trypanosomal diminazine aceturate (Berenil). LBP levels of the mice then decreased to pre-infection levels within one-week. This demonstrated that LBP is an acute phase protein during murine trypanosomosis. Furthermore, opportunistic secondary bacterial infection during trypanosomosis did not seem to play an important role in the changes in plasma LBP levels. We speculate that the marked concomitant increases in plasma LBP and endotoxin-like activity following murine trypanosome infection might play an important role in the pathogenesis of trypanosomosis.