The purpose of this study was to develop and pilot-test an interactive CD-ROM aimed at the prevention of sexually transmitted infections (STIs) in female adolescents. The CD-ROM includes prevention information, models skills for negotiating abstinence and consistent condom use, teaches media literacy, and allows the user to choose a culturally appropriate host to guide them through the CD-ROM. Forty-seven female adolescents attending a health department clinic were randomized to receive the CD-ROM plus an educator-led didactic session versus the didactic session alone. The CD-ROM was highly acceptable and feasible for use among female adolescents in the clinic setting. Hispanic and African American adolescents were more likely to choose hosts of the same race/ethnicity to guide them through the CD-ROM. HIV/STI knowledge increased significantly and nearly all adolescents intended to use condoms at next intercourse after viewing the CD-ROM. However, there were no significant differences measured between CD-ROM and comparison groups.