The number of cryopreserved human spermatozoa which penetrated zona-free hamster oocytes after stimulation with 2 mumol A23187 per litre was increased by the further addition of 0.6 or 3.6 mmol pentoxifylline per litre. With spermatozoa prepared by washing by repeated centrifugation, the median numbers of sperm heads/egg were 1.9, 7.9 and 10.8 in the presence of 0, 0.6 or 3.6 mmol pentoxifylline per litre, respectively. A similar effect was observed with spermatozoa prepared on a Percoll gradient. As A23187 inhibited sperm motility, and this was exacerbated by pentoxifylline, the increased penetration rate of hamster oocytes cannot be explained by improved sperm motility. The number of spermatozoa stimulated to acrosome react by 2 mumol A23187 per litre was increased 3-fold by 3.6 mmol pentoxifylline per litre and 4-fold by 5 mmol caffeine per litre. These data suggest that cAMP may act synergistically with Ca2+ to stimulate the acrosome reaction. Pentoxifylline may improve the fertility of poor-quality human spermatozoa by enhancing their ability to respond to the Ca2+ signal produced by binding to the zona pellucida.