In his otherwise excellent review of the AIDS epidemic in the 21st century, Fauci presented no new strategies for preventing the spread of the disease.1 He made no mention of male circumcision, yet there is now compelling epidemiological evidence from over 40 studies which shows that male circumcision provides significant protection against HIV infection; circumcised males are two to eight times less likely to become infected with HIV.2 Furthermore, circumcision also protects against other sexually transmitted infections, such as syphilis and gonorrhoea,3 4 and since people who have a sexually transmitted infection are two to five times more likely to become infected with HIV,5 circumcision may be even more protective. The most dramatic evidence of the protective effect of circumcision comes from a new study of couples in Uganda who had discordant HIV status; in this study the woman was HIV positive and her male partner was not.6 No new infections occurred among any of the 50 circumcised men over 30 months, whereas 40 of 137 uncircumcised men became infected during this time. Both groups had been given free access to HIV testing, intensive instruction about preventing infection, and free condoms (which were continuously available), but 89% of the men never used condoms, and condom use did not seem to influence the rate of transmission of HIV. These findings should focus the spotlight of scientific attention onto the foreskin. Why does its removal reduce a man's susceptibility to HIV infection?