Inherited deficiency of mannan-binding lectin (MBL) has been shown to predispose to infections. Conversely, it has also been suggested that MBL might facilitate the uptake of certain intracellular microbes. The aim of this study was to investigate whether MBL plays a role in the HIV and tuberculosis epidemics in Africa. Thus, the authors determined the MBL serum concentration in 173 HIV infected patients (150 with concomitant tuberculosis), 94 patients with tuberculosis without being HIV infected, and 113 controls from Tanzania. The frequency of MBL deficiency was significantly increased in HIV infected patients compared with controls (12.1% and 3.5%, respectively). The frequency of patients deficient of MBL did not differ between controls and HIV negative patients with tuberculosis. However, HIV negative patients with tuberculosis had significantly higher MBL levels than both controls and HIV infected patients with or without tuberculosis. These results indicate that low levels of MBL are associated with increased risk of sexually transmitted HIV infection in Africans. By contrast, high levels of MBL may be involved in the pathogenesis of tuberculosis in immunocompetent individuals.