We studied the spectrum of meningitis and impact of HIV infection retrospectively (8 months) and prospectively (4 months) in 284 adult patients with meningitis hospitalized in Soweto, South Africa. Tuberculous meningitis (TBM) was the most common cause of meningitis (25.4%) followed by acute bacterial meningitis (ABM; 22.5%), acute viral meningitis (14.1%) and cryptococcal meningitis (13%). The in-hospital mortality was > 40% in TBM, ABM, cryptococcal meningitis, the neurosurgery and the parameningeal/parenchymal groups. At least 37.3% of all patients were HIV-seropositive (only 67.9% of patients were tested). In at least 27% of the study group the meningitis was an AIDS-defining illness (TBM, cryptococcal meningitis). Only 56.2% of patients with ABM had positive cultures (CSF or blood), of which Streptococcus pneumoniae was by far the most frequently found organism (35.8%). The spectrum of meningitis in HIV-affected communities in Africa can be expected to change towards a predominance of TBM and cryptococcal meningitis.