Five out of 38 patients (13%) with metastatic renal cell carcinoma had mental deterioration 3 weeks to 13 months after the start of treatment with recombinant interferon alpha-C. Metastatic spread to the brain, paraneoplastic effect of the tumor on the central nervous system and other causes of dementia were excluded. Computed tomography of the brain in these patients was normal and the width of the cerebral sulci and ventricles did not correlate with the severity of dementia. Specific patterns of atrophy were not seen. General deterioration, assessed by the change in Karnofsky performance status, was associated with dementia. The dementia may have been caused by a neurotoxic effect of interferon.