We retrospectively reviewed microbiological data from a tertiary care hospital in Botswana, and found that Cryptococcus neoformans was cultured from 15% (193/1 307) of all cerebrospinal fluid (CSF) specimens submitted for analysis, making it the most common diagnosed cause of meningitis in this population. Moreover, almost 70% of CSF samples with significant lymphocytosis did not yield a pathogen, suggesting that many causes of lymphocytic meningitis go undiagnosed.