Natural resistance to African trypanosomiasis in certain Bos taurus cattle in West Africa, called trypanotolerance, may hold solutions for control of this economically crippling disease. Comparison of immune responses between trypanotolerant and trypanosusceptible cattle have shown some differences in antibody response, complement level and cytokine expression, but it is not known whether these differences are the cause of resistance. Two experiments were carried out to assess the contribution of the immune and haemopoietic systems to trypanotolerance. The production of haemopoietic chimaeras from trypanotolerant and susceptible twin calves and comparison of their responses after infection with singleton calves, allowed an assessment of the role of the haemopoietic system in trypanotolerance. An in vivo depletion of CD4 cells in the two breeds allowed an appraisal of the role of T and B lymphocytes in trypanotolerance. The results of the two experiments suggest that natural resistance comprises at least two mechanisms, an innate mechanism that controls parasite growth, and another, involving the haemopoietic system, that is able to limit anaemia. This supports the hypothesis that innate mechanisms in trypanotolerant cattle are more efficient in controlling disease, making them less reliant on antibody responses.