Histoplasma is a dimorphic pathogenic fungus wich causes human infection worldwide, mainly in ecuatorial countries [1]. In immunocompetent patients the most commun clinical manifestations consist in a lack of symptoms or a self-limited flu-like profile. However, disseminated histoplasmosis, wich represents the 0.05% of the acute infections, is observed in immunosuppressed patients (most of them HIV infected or treated with immunosuppressive drugs), and the illness manifestations are indistinguishable from tuberculosis. Central nervous system (CNS) involvement is exceptional and affects 5-10% of patients with disseminated illness and only 26 previous cases of meningitis caused by this microorganism were described in the last decade [2]. The majority of these patients are treated with nonnucleoside reverse-transcriptase inhibitors, and it is necessary to notice that interaction between this drugs and itraconazole (used in the prophylaxis of these infections) exists. Although this drug-drug interaction is really presumed, the international literature review using MEDLINE database and EMBASE (keywords: interaction ± itraconazole ± nonnucleoside ± reverse-transcriptase ± inhibitors) showed only 3 previous cases [3-5]. It is interesting to report here, because of its rareness, one case of acute meningitis due to Histoplasma, whose treatment and prophylaxis failed initially because of drug-drug interaction between itraconazole and nonnucleoside reverse-transcriptase inhibitors.