In children with congenital rubella infection the deficits remain stable; neurologic deterioration after the first few years of life is not believed to occur. We have encountered three patients with a definite or presumptive diagnosis of congenital rubella, in whom a progressive neurologic illness developed that began in the second decade and was characterized by spasticity, ataxia, intellectual deterioration, and seizures. High antibody titers to rubella virus in serum and spinal fluid were present in two, and all had increased cerebrospinal-fluid protein and gamma globulin. Extensive attempts to recover a virus from brain and body fluids were unsuccessful. The brains of two patients showed a widespread, progressive, subacute panencephalitis mainly affecting white matter. These data suggest that rubella virus may be a cause of progressive panencephalitis.