In a prospective observational study of 54 patients with human immunodeficiency virus–associated cryptococcal meningitis, the early fungicidal activity of amphotericin B (1 mg/kg/day) was significantly greater than that of fluconazole (400 mg/day). Compared with antiretroviral therapy–naive patients, patients developing cryptococcal meningitis while already receiving antiretroviral therapy had lower baseline fungal burdens and a longer median duration of survival, but there were no differences observed in fungal clearance, cerebrospinal fluid proinflammatory cytokines, or 10-week mortality.