We conducted a 2-year investigation of the extent to which strategies based on social marketing and diffusion of innovations concepts are used in preventive health communication with unique (highly ostracized) populations. Of the 49 organizations in San Francisco that operate HIV prevention programs (N = 100), programs that most highly targeted unique populations were surveyed. Personal interviews were then conducted with 38 staff leaders who operated the most and least effective programs. Audiotapes and transcripts were content analyzed to identify the strategies used by program staff. Strategies based on social marketing concepts were more prevalent than strategies based on the diffusion of innovations: More effective programs were characterized by emphasis on homophily, audience segmentation, compatibility-based strategies, and interorganizational collaboration.