Mechanisms involved with human immunodeficiency virus type I (HIV-1) sexual transmission are not fully defined. We have demonstrated that endogenous reverse transcription of lenti-viruses can occur within the intact virion. This takes place before direct infection of the target cells. In a biochemically active process, endogenous reverse transcription occurs in HIV-1 virions in specific microenvironments. In virions without non-physiological permeabilization, endogenous reverse transcription can occur and has been entitled natural endogenous reverse transcription (NERT). This molecular mechanism dramatically increases HIV-1 infection in initially-quiescent peripheral blood mononuclear cells, as well as non-proliferating cells such as macrophages. This molecular process may augment sexually transmission of HIV-1, as HIV virion particles in genital secretions are shown to have increased endogenous reverse transcripts and NERT is potently stimulated. Further studies are necessary to determine whether this molecular mechanism is critical in vivo for sexual transmission of this human lenti-viral agent.