The typical absence of immune responses to spermatozoa in the female reproductive tract at the time of insemination, despite the presence of a marked leukocytic infiltrate into the cervical mucus is intriguing. It may be that localised immunoregulatory mechanisms exist and this study used whole blood flow cytometry to determine the effects of human seminal plasma on neutrophil and monocyte function. Seminal plasma inhibited the proportion of neutrophils and monocytes phagocytosing E. coli, and the intensity of neutrophil phagocytosis, but enhanced the magnitude of the phagocytic response of those monocytes that escaped inhibition relative to PBS treated controls. Oxidative burst responses to E. coli were also inhibited and this effect was mediated by low molecular weight species, as dialysis totally abrogated the inhibitory activity. Seminal plasma had no effect on the neutrophil burst response to fMLP when compared to the controls, however there was a significant difference between the responses of undialysed and dialysed seminal plasma treated samples. Undialysed seminal plasma significantly inhibited the proportion of monocytes undergoing the burst response to fMLP and there were significant differences between the proportion of cells responding and their intensity in undialysed and dialysed seminal plasma treated samples. In summary, this study reports differential modification of neutrophil and monocyte function by human seminal plasma. The residual capacity of these cells to undergo phagocytosis and generate oxidative burst responses suggests that localised innate immune function remains intact and is possibly enhanced in the female reproductive tract at the time of insemination. Other mechanisms must protect inseminated sperm at this time.