The need for standardized operational definitions, as well as a more sensitive, easily applied, and reproducible upper extremity functional assessment for following patients in multiple sclerosis clinical trials is evident. Experience with the use of two upper extremity functional assessment instruments--the nine-hole peg test (9HPT) and the box-and-block test (BBT)--is described. The patients, who were followed for six months, experienced subjective change in functional status but failed to show significant change on the pyramidal, cerebellar, or visual functional scores of the Kurtzke Expanded Disability Status Scale (EDSS). The prevalence of upper extremity dysfunction in multiple sclerosis, as measured by the 9HPT and the BBT, is higher than previously appreciated. The 9HPT and BBT are more sensitive in detecting upper extremity functional status change than the EDSS and should prove helpful in following patients in clinical trials.