Nervous system opportunistic infections are seen in about one fifth of AIDS cases and account for over 40% of the patients with neurological manifestations. Serious infections are seen in severely immunosuppressed patients, usually with CD4 counts of 200 ml-1 or less. The commonest is CMV, which can produce acute encephalitis, sometimes with focal hemisphere or brain-stem signs, dementia, retinitis, optic neuritis and an ascending radiculomyeloencephalitis. Cryptococcal meningitis is the most frequent fungal disease; a high degree of clinical suspicion is required in patients with fever, malaise, headache or seizures. Only CSF cultures are always positive; both serum and CSF cryptococcal antigen tests are highly sensitive and specific. Treatment with amphotericin B and flucytosine is successful in at least 70% of first episodes but side-effects are common. Without maintenance therapy 50% of patients relapse; fluconazole is recommended. Cerebral toxoplasmosis can present with focal cerebral or spinal cord signs but also as a diffuse encephalopathy; negative T. gondii serology is exceptional but positive serum titres are usually unhelpful. Treatment with sulfadiazine, pyrimethamine and folinic acid achieves good results in 90% of the first episodes, but side-effects are common. Appearances on CT scan or MRI may take several weeks to improve. The value of an empirical approach to treatment is well-established; an initial cerebral biopsy is difficult to justify. Without maintenance therapy a relapse rate of 50% can be expected; therapy with sulfadiazine and pyrimethamine may also prevent pneumocystosis. HIV disease appears to increase the likelihood of neurosyphilis, and the risk of relapse after conventional penicillin doses, in patients with syphilis; at least 3-4 weeks of appropriate therapy are recommended. A number of other diseases caused by viruses, fungi, bacteria and parasites are less common; these include progressive multifocal leukoencephalopathy, herpes simplex and zoster infections and tuberculosis.