A recently isolated human strain of Trypanosoma rhodesiense (EATRO No. 1886) from Uganda was infective for mice and rhesus monkeys. Mice receiving two or three immunizing inoculations of gamma-irradiated trypanosomes were markedly protected from a challenge infection of 1,000 unirradiated organisms 1 week after immunization. Complete protection from a challenge infection was induced in 5 of 6 monkeys given six immunizing inoculations with irradiated trypanosomes. Conversely, the five unimmunized controls became patent 5 to 8 days after challenge with 10,000 unirradiated organisms, showed signs of progressive severe illness, and died between 12 and 49 days after challenge.