A case of an isolated impairment of the ability of acrosome-reacted spermatozoa to fuse with the oocyte is reported. This impairment was associated with fertilization failure after subzonal sperm insertion even though elevated numbers of spermatozoa were inserted per oocyte. This observation shows the need for further studies into the relationship between the acrosome reaction and the sperm-oocyte fusion to better understand the advantages and the limitations of subzonal sperm insertion in different types of sperm pathology.