Self-report of sexual orientation and sexual behavior was compared for 12,978 reservation-based American-Indian and 11,356 rural Anglo-American adolescents. Findings included a significantly higher prevalence of homosexual, bisexual, and unsure responses among American Indians. However, a larger nonresponse rate for American-Indian adolescents raises questions about the cultural relevance of the survey method, and underscores the need for development of more culturally sensitive research tools and methods.