Six AIDS patients with progressive cytomegalovirus (CMV) polyradiculomyelitis were treated with ganciclovir in an open study. The diagnosis was based on the presence of a distinct clinical syndrome with progressive flaccid paraparesis, preserved proprioception and urinary retention with specific cerebrospinal fluid (CSF) findings. Ganciclovir therapy, 5-10 mg/kg per day, instituted 3-6.5 weeks after onset of symptoms, was ineffective in four patients with severe paraparesis. One patient developed CMV polyradiculomyelitis while receiving ganciclovir and further deteriorated during foscarnet therapy. One patient however, showing minor paresis of one leg, improved after institution of ganciclovir therapy 1 week after onset of symptoms. It is concluded that a presumptive diagnosis of CMV polyradiculomyelitis can be made on the basis of distinct clinical findings and CSF pleocytosis with predominance of polymorphonuclear leukocytes in patients with AIDS. Ganciclovir therapy does not appear to be beneficial for patients with advanced paresis in the doses used. Further investigations are needed in order to determine if early intervention with ganciclovir, when paresis is mild, or higher doses in advanced paresis, might be of some benefit.