Although most current stroke intervention trials use disability scales to determine outcome, little is known about the sensitivity to change of these scales. The use of a more sensitive measure would increase the statistical power of rehabilitation treatment trials. We applied four well-known disability scales to a group of stroke rehabilitation inpatients to compare sensitivity to change. Ninety-five consecutive admissions to a stroke rehabilitation service were assessed for disability on admission and discharge. Two global scales, the Modified Rankin Scale (MRS) and the International Stroke Trial Measure (ISTM), were compared with two activities of daily living (ADL) scales, the Barthel Index (BI) and the Functional Independence Measure (FIM). We determined the number of patients that each scale detected a clinically significant change in disability. Standardized response means (SRM) and receiver operating characteristic (ROC) analyses were performed. The MRS detected change in 55 subjects, including all who changed on the ISTM; the ISTM detected change in only 23 subjects. The BI detected change in 71 subjects but demonstrated ceiling effects with 26% of subjects scoring >95. The FIM was most sensitive, detecting change in 91 subjects; no patient achieved a maximum score. The SRM of the FIM was superior to that of the BI (2.18 versus 1.72), and ROC analysis revealed C-statistics of 0.82 for the BI, 0.59 for the MRS, and 0.51 for the ISTM. Global scales were much less sensitive to changes in disability than were ADL scales. Though ADL scales may take longer to administer, their increased sensitivity may make them more useful in treatment trials by allowing fewer subjects to be enrolled.