Distal sensory peripheral neuropathy (DSPN) has been reported in 5 to 75% of patients with human immunodeficiency virus (HIV) infection, particularly in advanced stages of the disease. Twenty HIV seropositive patients were studied prospectively to determine the frequency of DSPN in clinical stage II and III of the HIV infection, and to investigate the role of vitamin B12 deficiency on the frequency of DSPN in HIV patients. All patients had complete blood count, serum vitamin B12 level, anti-intrinsic factor antibody, Schilling test, and electrodiagnostic studies including nerve conduction studies and concentric needle examination in the lower extremities, and sympathetic skin responses. Only 1 patient (5%) had clinical and electrophysiological evidence of possible DSPN. Of the 6 patients with abnormal Schilling test, only one had DSPN based on distal sensory symptoms, abnormal neurological examination and electrodiagnostic studies. Evidence for possible DSPN was present in 5% of patients with early HIV infection and did not appear to be more frequent in patients with concurrent vitamin B12 deficiency.