The advent of the use of structured interview schedules that generate psychiatric diagnoses in epidemiologic studies has promoted an intense interest in its cross-cultural use. However, the valid use of these instruments across cultures requires a careful adaptation process which goes beyond mere language translation. In this article the authors illustrate the application of a comprehensive cross-cultural adaptation model to both the translation into Spanish and the adaptation to the population of Puerto Rico of a widely used psychiatric epidemiologic research instrument: the Diagnostic Interview Schedule (DIS). The process aimed to ensure the development of a research instrument that is not only in correct Spanish and comprehensible for most Spanish-speaking people, but also culturally adapted to Puerto Rico's population. Various steps were taken (including bilingual committee, back-translation, instrument testing and diagnostic comparisons) to address cross-cultural validity in five important dimensions (i.e., semantic, technical, content, criterion and conceptual equivalence). The result is an interview schedule that is not only linguistically and culturally adequate for the targeted population but also includes elements which can contribute to the development of the instrument both in its original English language and in its translated versions.