Surfactant protein A (SP-A), first identified as a component of the lung surfactant system, is now recognized to be an important contributor to host defence mechanisms. SP-A can facilitate phagocytosis by opsonizing bacteria, fungi and viruses, stimulate the oxidative burst by phagocytes and modulate pro-inflammatory cytokine production by phagocytic cells. SP-A can also provide a link between innate and adaptive immune responses by promoting differentiation and chemotaxis of dendritic cells. Because of the obvious relevance of these mechanisms to the host defence and 'gate keeping' functions of the lower genital tract, we examined human vaginal mucosa for SP-A protein and transcripts and analysed vaginal lavage fluid for SP-A. By immunocytochemistry, SP-A was identified in two layers of the vaginal epithelium: the deep intermediate layer (the site of newly differentiated epithelial cells); and the superficial layer (comprising dead epithelial cells), where SP-A is probably extracellular and associated with a glycocalyx. Transcripts of SP-A were identified by Northern blot analysis in RNA isolated from vaginal wall and shown, by sequencing of reverse transcription-polymerase chain reaction products, to be derived from each of the two closely related SP-A genes, SP-A1 and SP-A2. SP-A was identified in vaginal lavage fluid by two-dimensional gel electrophoresis, and confirmed by mass spectrometry. This study provides evidence, for the first time, that SP-A is produced in a squamous epithelium, namely the vaginal mucosa, and has a localization that would allow it to contribute to both the innate and adaptive immune response. The findings support the hypothesis that in the vagina, as in lung, SP-A is an essential component of the host-defence system. A corollary hypothesis is that qualitative and quantitative alterations of normal SP-A may play a role in the pathogenesis of lower genital tract inflammatory conditions.