Infection by human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), a debilitating disorder in which progressive weakening of the immune system makes affected individuals more susceptible to potentially life-threatening infections and chronic diseases. Despite advances in the treatment and management of AIDS, there is no cure, and HIV infection remains a major global health problem. According to the WHO, there were an estimated 34 million infected individuals in 2011. Over the last three decades, a number of animal models have been developed to study aspects of HIV infection, pathogenesis and control. However, the currently available models do not recapitulate the physiological environment of the most common route of HIV transmission worldwide, vaginal intercourse. Now, Mary Jane Potash and colleagues from St. Luke's-Roosevelt Hospital Center and Columbia University Medical Center in New York, NY, have developed an approach for modelling heterosexual transmission of HIV in vivo. Their work was published recently in Disease Models & Mechanisms.