In this study we evaluated and compared the inter-rater variabilities in detecting enhancing lesions in patients with MS after injection of a standard dose (s.d.) and a triple dose (TD) of gadolinium (Gd). Enhanced magnetic resonance imaging (MRI) were obtained in 15 patients, consisting of T1-weighted images 5 to 7 min after the injection of the s.d. (0.1 mmol/kg) of Gd and, after an interval of 6 to 24 h, 5 to 7 min after the injection of the TD (0.3 mmol/kg). An additional scan 1 h after the TD injection (delayed scanning-DS) was obtained in 11 patients. The scans were independently evaluated in a random order by four observers. Lesions were counted and scored according to size and location. The level of inter-observer observer concordance was very high for reporting the total numbers of enhancing lesions, their sizes and sites for the three experimental conditions. No significant differences were found in inter-observer variability in reporting the total number of enhancing lesions and their location in different brain sites in the three conditions. Our data indicate that the gain in sensitivity in detecting enhancing lesions in MS with the TD is not counteracted by a loss in reproducibility. This is important in planning clinical trials in which the number of enhancing lesions is used as a measure of outcome.