Laboratory-bred rodents of three species were inoculated with heterologousHerpetosoma trypanosome species as follows:Microtus agrestis withTrypanosoma evotomys orT. grosi, Apodemus sylvaticus withT. evotomys orT. microti andClethrionomys glareolus withT. grosi orT. microti. The three rodent species were subsequently challenged with their natural trypanosome parasite, i.e.T. microti forM. agrestis, T. grosi forA. sylvaticus andT. evotomys forC. glareolus. The parasitaemias and courses of infection that developed were followed. All challenged animals showed some degree of cross-immunity; not all became infected, and those that did had lower levels of parasitaemia and shorter patent periods than control animals. NoC. glareolus previously inoculated withT. microti developedT. evotomys infections on challenge, and an infection was observed in just one of tenM. agrestis inoculated first withT. evotomys and later withT. microti.