A fatal case of disseminated granulomatous infection with a skin lesion and focal encephalitis due to Acanthamoeba astronyxis is reported. Indirect fluorescent antibody tests of both tissue and serum from the patient established the diagnosis. The administration of amphotericin B is ineffective in vitro and has not been effective in vivo. It is recommended that corticosteroid therapy be avoided because it may aggravate the disease. Physicians caring for diseases caused by free-living ameba may call the CDC Parasitic Drug Service.