Cryptococcus neoformans commonly causes opportunistic infection in immunocompromised patients, especially in patients with AIDS. The CD4+ T-lymphocyte count is measured in patients with HIV infection, because it signals an increased risk of opportunistic infection and a decline in immunological function. We report a case of cryptococcal meningitis in a patient with persistently low CD4+ cell counts without evidence of HIV infection. The patient's underlying immunocompromised state was attributed to idiopathic CD4+ T-lymphocytopenia (ICL), a recently described syndrome characterized by depletions in the CD4+ T-cell subsets without evidence of HIV infection. Immunodeficiency can exist in the absence of laboratory evidence of HIV infection, highlighting the importance of evaluating T-cell subsets in patients who present with unusual infections.