Cryptococcal disease in HIV-positive individuals is usually a consequence of advanced immunosuppression. Treatment consists of long period of induction therapy followed by long-term secondary prophylaxis, usually with fluconazole. The introduction of highly active antiretroviral therapy has resulted in improvements in immunological function such that the cessation of primary and secondary prophylaxis against several opportunistic infections has become possible. We report our experience of the cessation of secondary antifungal prophylaxis in patients responding to highly active antiretroviral therapy.