 Twelve hundred healthy, sexually active women and men, 18-29 years old, without HIV infection will be enrolled in Francistown and Gaborone, Botswana. They will be provided with free male and female condoms, repeated individualized risk-reduction counseling, diagnosis and treatment of sexually transmitted diseases, and women will be provided with a choice of effective family planning methods. In addition, volunteers will be randomized to receive either Tenofovir or a placebo pill to take once a day. Volunteers will be seen monthly for at least 12 months to monitor for side effects and toxicities and to test their HIV status. Persons who become HIV infected during the trial will receive ongoing supportive counseling, CD4 and viral load monitoring, education about HIV infectiondisease, and access to HIV care including free antiretrovirals when clinically indicated. Volunteer safety will be monitored by a local ethics committee, Centers for Disease Control Institutional Review Board CDC IRB and an independent data safety and monitoring board. 