With the increase of QoL assessment in clinical trials, it is necessary to have cross-culturally valid instruments to pool data across countries. The FAMS, a 59-item instrument designed in US English assesses 6 domains of multiple sclerosis. Prior to use in an international trial, it had to undergo cross-cultural adaptation in 9 languages. This involved the recruitment of a QoL specialist in each target country. Two independent forward translations were produced by native speakers, were reconciled and then backtranslated into English. The translations were tested for comprehension in a sample target population, compared and internationally harmonized. The developer clarified concepts underlying each item. Translation problems involved finding conceptual equivalents of typical US expressions and the response categories. For example, a literal translation of the term "social activity" referring to humanitarian work in certain languages, required a descriptive equivalent. Translating "getting around in public places" necessitated lengthy descriptions in certain languages to retain the original concept. The neutral term "condition" could not be retained in certain translations where the reference to "health state" or even "illness" was the best compromise. Patient testing showed that a response option "not applicable" was lacking and that answers should refer more clearly to the introductory sentence. To harmonize with the validated original however, no changes were made in the response categories. Prior to use in an international trial, rigorous cultural adaptation was essential in producing cross culturally valid language versions. The integration of changes to the responses in an updated form of the instrument might require further validation. Further responsiveness data will be generated by the clinical trial. Ideally initial instrument design should include international input.