Administration of neutralizing anti-TNF alpha antibodies did not prevent Plasmodium berghei induced cerebral malaria (CM) in C57Bl/6 mice, when given at different dosages and time intervals. Elevated concentrations of immunoreactive TNF alpha were found in the circulation but no bioactive TNF alpha could be detected in mice developing CM. Furthermore, elevated TNF alpha receptor concentrations were measured in the plasma of mice developing CM. Plasma of these mice neutralized bioactive recombinant-mouse TNF alpha indicating that a part of the plasma TNF alpha-receptors were not complexed with TNF alpha. The apparent absence of free TNF alpha probably explains why treatment with antibodies against TNF alpha failed to prevent development of CM.