Objective: To determine the effects of immunodeficiency, nutritional status, and concurrent systemic disease on peripheral nerve function in acquired immunodeficiency syndrome. Design: Survey of subjects infected with human immunodeficiency virus (HIV), recruited as part of a prospective study of neuromuscular complications of HIV infection. Setting: A neuro-acquired immunodeficiency syndrome outpatient clinic in a university medical center. Patients: A consecutive sample of 251 HIV-infected individuals. Primary care providers referred subjects to the study for evaluation of neurologic symptoms or for prospective neurologic assessment. Main Outcome Measures: Standardized history and neurologic examination, laboratory tests (complete blood cell count, serum albumin level, vitamin B12 level, and T-lymphocyte subsets), and electrophysiologic testing of sural, tibial, and ulnar nerves. Results: The most frequent neurologic diagnosis was distal symmetrical polyneuropathy (DSP) (38%). The most common clinical features were nonpainful paresthesias (71%), abnormalities of pain and temperature perception (71%), and reduced or absent ankle reflexes (66%). Patients with DSP were significantly older (P = .009), and had lower CD4 lymphocyte cell counts (P = .004) and lower hemoglobin levels (P = .004) than those without DSP. Deterioration of values on nerve conduction studies, irrespective of the clinical diagnosis of DSP, was significantly correlated with low CD4 counts, aging, abnormal serum albumin and hemoglobin levels, and weight loss. Most of these factors co-correlated, and, with the exception of age, no single variable significantly accounted for changes in results of nerve conduction studies when the influence of other factors was eliminated. Conclusion: The combination of several factors, including age, immunosuppression, nutritional status, and chronic disease, contributes to distal peripheral nerve dysfunction in HIV infection.