( P) is one of the physiolog ical stimuli of human sperm acrosome reaction. It is present u P rog esterone in hig h levels at the site of f ertilization ( cumulus oophorus) and has been descr ibed to aÚ ect several sperm f unctions including motility, capacitation and acrosome reaction. T he eÚ ects of the steroid, which is present in hig h levels in the cumulus matrix that surrounds the oocyte, are mediated by an increase of intracellular calcium concentrations, ef f lux of chloride, stimulation of activity of phosphol ipases and phosphor ylation of proteins. T hese eÚects are due to activation of a rapid/nong enom ic pathw ay. T wo diÚ erent types of receptors for P, distinct from the g enomic ones, have been recently identi ed on the surface of human spermatozoa. T he af finities of P for these receptors are respectively in the nano-and in the micromolar rang e. Sper m responsiveness to prog esterone is impaired in subf ertile patients and is strictly correlated to the ability of fertilizing the oocyte. In addition, the determination of sperm responsiveness is predictive of f ertilizing ability with a positive predictive value of 90% and can be clinically usef ul for the preliminary assessment of the male par tner to select the appr opriate assisted reproductive technique.