Adolescents with high-functioning autism (HFA) possess core social and pragmatic deficits, which interfere with normal relationship development. At a time when friendships are increasingly important, many adolescents with HFA realize they are different from their peers. Initial research has indicated that adolescence is the time when symptoms of anxiety and depression are most likely to develop. The purpose of this study was to increase knowledge about anxiety and depression in HFA through focusing on the adolescent development period and obtaining assessment information from multiple sources. Results indicate that adolescents reported elevated levels of social anxiety, separation panic, and anhedonia compared with normative samples. Parents and teachers reported that adolescents experienced significant overall anxiety and depressive symptomatology compared with the normative samples. Manifestations of HFA were associated with higher levels of anxiety as reported by parents. Results bring into question the validity of self-report scales for adolescents with HFA in the ability to accurately self-report and in the measures' capacity to differentiate between internalizing symptoms and core HFA behaviors.