Leishmaniasis has emerged as an important potential opportunistic disease among patients infected with human immunodeficiency virus type-1 (HIV-1). It has been reported that the visceral form of leishmaniasis accelerates the course of HIV-1 disease progression and shortens the life expectancy of persons in areas where both diseases are endemic. As both pathogens can infect in a productive manner the same target cell, that is, the macrophage, we examined the possible modulatory effect of the protozoan parasite Leishmania infantum on the biology of HIV-1 in primary human monocyte-derived macrophages (MDMs). We found that coinfection of MDMs with Leishmania and HIV-1 resulted in a significant enhancement of both virus transcription and release of progeny virus. The Leishmania-directed increase in HIV-1 production was associated with an increased secretion of the proinflammatory cytokines TNF-alpha and IL-1 alpha. Altogether, these findings indicate that the presence of Leishmania and HIV-1 within the same cellular microenvironment leads to an enhancement of virus gene expression. The present work also underscores the importance of studying the possible complex interactions between two human pathogens in a physiological cellular reservoir.