Heterosexual transmission of HIV-1 is likely to involve transmission of virus present in seminal fluid to inflammatory cells, particularly macrophages, present in the endometrium and peritoneal cavity. We have investigated the susceptibility of peritoneal macrophages and the corresponding autologous blood monocytes from normal women to infection by the BA-L strain of HIV-1. In 10 of 18 examples, peritoneal macrophages showed signs of infection within 4-5 days, which was earlier than the autologous monocytes. In contrast to peritoneal macrophages, lung macrophages from 10 of 11 normal donors failed to show significant reverse transcriptase (RT) values 3 weeks post infection. Monolayer cultures of monocytes cultured for 5 days prior to infection developed RT values similar overall to those of freshly isolated cells although individual donors varied as to which culture condition was optimal. The ease of infection of peritoneal macrophages did not correlate with levels of CD4 antigen or degree of pelvic inflammatory development, nor were macrophages harvested from women early in the menstrual cycle significantly more susceptible to infection than those collected from midcycle on. This unexplained heightened infectibility of peritoneal macrophages in a proportion of normal women suggests that those individuals could be more at risk for heterosexual transmission of HIV-1 infection.