Painful peripheral neuropathy is not only a devastating manifestation of HIV infection but also seriously limits potentially life-saving nucleoside therapy. Recent work conclusively has demonstrated that individuals with pre-existing nerve disease are substantially pre-disposed to developing earlier and more severe toxic neuropathies from nucleoside agents. Studies of nucleoside efficacy, to date, have involved only homosexual patients. These studies have resulted in an understanding of the nature of the toxic neuropathy and the relationship of pre-existing nerve disease, in the homosexual population, to nucleoside induced neuropathy. This knowledge has allowed the development of alternative dosing regimens aimed at reducing neuropathic complications. The continued promising results of these studies suggest that these agents will soon need to be administered to a wide range of HIV infected patients, most notably, intravenous drug abusers (IVDAs). Unfortunately, there is no data on the prevalence of nerve disease in non-infected and infected IVDAs to guide nucleoside therapy in IVDAs or to predict the likelihood of toxic complications. We propose a 3 year prospective study of IVDAs, primarily recruited from a methadone clinic to: 1) determine the baseline prevalence of peripheral neuropathy in non-infected subjects, and HIV infected IVDAs in the asymptomatic, ARC and AIDS stages, 2) characterize the nature of the neuropathy and 3) identify the factors important in the progression of the above neuropathies by following patients over a 3 year period. To accomplish this, individuals in various stages of HIV infection will undergo a comprehensive neuropathy evaluation which includes questionnaire, physical examination, quantitative sensory testing and nerve conduction studies. Knowledge gained from this study will be invaluable in formulating intelligent treatment strategies for nucleoside therapy in the IVDA population. The research team and patient recruiting opportunities are ideally suited for this project. We have experience in both HIV and toxic nerve disease and the availability of an extensively studied compliant IVDA population already enrolled in a longitudinal study of HIV infection in our methadone program.