There are few peer-reviewed studies of HIV/AIDS-related knowledge, attitudes, beliefs and practices among adolescents in Central America. A population-based cross-sectional survey was conducted among 246 adolescents in León, Nicaragua, where there is reason for concern about a rise in HIV infections. In many respects, León adolescents were typical of those in other Latin American countries, with a mixture of correct and incorrect knowledge about transmission of HIV and sexually transmitted infections, a higher proportion of males than females reporting having had sex or using condoms, and inconsistent condom use. While some sexual attitudes conformed to the ideology of machismo, others did not, providing an opening for prevention interventions. Some dimensions of HIV/AIDS stigma were high, and most adolescents disapproved of same-sex sexual behaviour. Intervention against homosexuality-related stigma is particularly urgent because a concentrated HIV epidemic may be emerging in Nicaragua among men who have sex with men. Personal religious beliefs did not appear to pose a barrier to condom use. In a multivariate model, being out of school was a significant correlate of having had sex and of insufficient HIV/AIDS-related knowledge. Accordingly, HIV prevention interventions must reach adolescents both in and out of school. A multi-component approach to prevention is needed, including programmes based in schools, communities, the mass media and health facilities.