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Determining rates of HIV transmission risk behavior among HIV-positive individuals is a public health priority, especially as infected persons live longer because of improved medical treatments. Few studies have assessed the potential for transmission to the partners of HIV-positive persons who engage in high-risk activities. A total of 3723 HIV-infected persons (1918 men who have sex with men [MSM], 978 women, and 827 heterosexual men) were interviewed in clinics and community-based agencies in Los Angeles, Milwaukee, New York City, and San Francisco from June 2000 to January 2002 regarding sexual and drug use behaviors that confer risk for transmitting HIV. Less than one quarter of women and heterosexual men had 2 or more sexual partners, whereas 59% of MSM reported having multiple partners. Most unprotected vaginal and anal sexual activity took place in the context of relationships with other HIV-positive individuals. Approximately 19% of women, 15.6% of MSM, and 13.1% of heterosexual men engaged in unprotected vaginal or anal intercourse with partners who were HIV-negative or whose serostatus was unknown. The majority of sexually active participants disclosed their serostatus to all partners with whom they engaged in unprotected intercourse. An estimated 30.4 new infections (79.7% as a result of sexual interactions with MSM) would be expected among the sex partners of study participants during the 3-month reporting period. Eighteen percent of 304 participants who injected drugs in the past 3 months reported lending their used injection equipment to others. In addition to the more traditional approaches of HIV test counseling and of focusing on persons not infected, intensive prevention programs for persons with HIV infection are needed to stem the future spread of the virus.