Neuropathic complaints were frequently observed in a Phase I study of dideoxyinosine (ddI) in 44 patients with AIDS and AIDS-related complex. Ten patients (23%) were thought to have a ddI-related peripheral neuropathy. The symptoms were primarily sensory, and there was limited motor involvement. The sensory symptoms improved in all patients with discontinuation of ddI. Some patients tolerated reintroduction of ddI at lower doses without significant recurrence of the neuropathic symptoms. Although the neuropathy was usually seen in patients taking higher doses of ddI than used in current treatment protocols, clinicians must be aware of this potential toxicity as more human immunodeficiency virus-infected patients are being treated with ddI.