Results reported here show that humans have various levels of trypanocidal activity in their sera. This difference appeared stable when different samples were taken from the same individuals over time. It was not possible to account for the variability between individuals by obvious differences in health, nutrition, or living habits. In addition, the trypanocidal titers did not vary significantly when stored for various lengths of time at -70 C. To examine the relationship between the titer of trypanocidal activity in a host and the degree of human serum resistance of the challenge trypanosome inoculum, mice (C57BL/6J) were pretreated with various amounts of different human serum and then infected with clones having different degrees of resistance to human serum. It was demonstrated that host susceptibility to an African trypanosome infection depends upon 2 variables: the level of trypanocidal activity in individual human serum and the degree of human serum resistance of individual clones of African trypanosomes. Based upon the animal model presented here, it is hypothesized that this relationship is under selective evolutionary pressure and will influence the susceptibility of animals in endemic areas as well as the transmission of human trypanosomiasis.