Anti-sperm antibodies in semen have been associated with a decrease in fertility potential. The question arises as to whether intra-uterine insemination (IUI) can improve pregnancy rates by merely allowing earlier capacitation and close timing to ovulation, or whether certain treatments of the spermatozoa add extra benefit. The study presented herein was designed to compare IUI using Percoll density separation with an albumin treatment versus chymotrypsin/galactose treatment. Sixteen patients were evaluated where IUI was randomized between both sperm treatments. Pregnancy rates/cycle were 25% (eight of 32) with chymotrypsin/galactose-treated spermatozoa compared to only 3% (one of 33) cycles with albumin-treated spermatozoa (P < 0.01). Since it has been reported that the proportions of spermatozoa showing immunobead binding for specific antibodies after chymotrypsin/galactose treatment remain unchanged, the exact mechanism for improvement is unknown; possibly chymotrypsin/galactose interferes with the function of the antibodies.