Although human T-cell leukemia virus (HTLV) type I is known to cause a number of diseases, there has been no convincing evidence of pathological changes after infection with the related virus, HTLV-II. We have found an endemic focus of HTLV-II infection among members of an American Indian population in New Mexico, USA. We set out to determine the pathological consequences of HTLV-II infection in this population and identified two sisters (aged 59 and 46 years) with a disease superficially resembling the myeloneuropathy induced by HTLV-I. These women had a syndrome similar to the olivopontocerebellar atrophy variant of multiple system atrophy, and HTLV-II infection was confirmed by western blot and the polymerase chain reaction. Thus, HTLV-II may, like HTLV-I, cause a progressive neurodegenerative disease.