New immunomodulatory therapies for relapsing-remitting multiple sclerosis (RRMS) have well-documented effects in reducing relapses, but it has been difficult to demonstrate their benefits on disability in relatively short treatment trials. Commonly utilised disability outcome measures are problematic both in usefulness and clinical interpretation when applied to MS subjects with fluctuating and variable disease courses. An alternative technique is to use the summary measure 'area under the disability/time curve' (AUC) to index the total in-trial morbidity experienced by patients. In this study, we applied AUC analyses to the serial Expanded Disability Status Scale (EDSS) scores from the U.S. multicentre, Phase III, two-year core study of glatiramer acetate in 251 RRMS patients. When all available EDSS evaluations were analysed with AUC(CHANGE) ('combined data', including relapse-related assessments), active treatment was significantly superior to placebo (P=0.018). The benefits of glatiramer acetate persisted when transient relapse effects were reduced by using 'scheduled visit data' only (P=0.021). With the more conservative AUC(SUM) measure, significant active treatment effects remained (P=0.029 and 0.046, for both 'combined' and 'scheduled visit' data, respectively). Subgroup calculations performed with baseline disability stratified at EDSS 3.5 also showed benefits of treatment over placebo, but statistical significance was not reached. This analysis of data from a Phase III treatment trial illustrates the AUC summary measure technique and provides further evidence of the efficacy of glatiramer acetate in RRMS.