In up to 50% of all human immunodeficiency virus (HIV) patients, the nervous system is clinically involved. Primary or secondary manifestations of the nervous system have been found in even 90% by neuropathological investigations. We present a retrospective analysis of cerebrospinal fluid (CSF) and serum data of 238 HIV patients. Data of cross-sectional analysis in 208 patients and longitudinal analysis in 30 patients are given. In addition, the viral load in CSF and serum was determined in 29 patients. The HIV patients without opportunistic infections showed increased levels of immunoglobulins and more oligoclonal bands. In later stages of the infection, beta-2 microglobulin as a marker of HIV-associated encephalopathy was increased. In the longitudinal study with an observation period of 1 year, an increase could be observed in total CSF proteins of patients who did not receive antiretroviral treatment. In patients with new opportunistic infections of the central nervous system, similar changes in CSF parameters were noted as in comparison to patients not infected by HIV but with the same opportunistic infections. Analysis of CSF is mandatory for the diagnosis and control of opportunistic infections.