We reviewed the records and radiologic studies of eight patients who developed new focal neurologic abnormalities while receiving interleukin-2 (IL2)-based immunotherapy for malignancy or HIV infection. Initial confusion and delirium in the patients evolved into coma, ataxia, hemiparesis, seizures, and cortical syndromes including aphasia, apraxia, and cortical blindness. Imaging studies showed multiple white and gray matter lesions with a predilection for the occipital poles, centrum semiovale, and cerebellum. After cessation of IL2 treatment, seven patients improved to normal or near-normal neurologic function paralleled by resolution of the lesions on scans. One patient improved only minimally. Possible etiologies for the lesions include an IL2-induced cerebral vasculopathy, a direct toxic effect of IL2, or immunologically mediated damage.