Fast spin echo (FSE) and fast fluid attenuated inversion recovery (fast-FLAIR) MR sequences were compared with conventional spin echo (CSE) in quantitating multiple sclerosis (MS) lesion burden. For each sequence, the total number and volume of MS lesions were calculated in 38 remitting MS patients using a semiautomated lesion detection program. CSE, FSE and fast-FLAIR images were reported on randomly and at different times by two expert observers. Interobserver differences, the time needed to quantitate MS lesions and lesion signal intensity (contrast-to-noise ratio and overall contrast) were considered. The lesions were classified by site into infratentorial, white matter and cortical/subcortical. A total of 2970 lesions with a volume of 961.7 cm3 was calculated on CSE images. FSE images depicted fewer (16.6%; p < .005) and smaller (24.9%; p < .0001) lesions and the differences were statistically significant. Despite an overall nonsignificant reduction for fast-FLAIR images (.5% and 4.8% for lesion number and volume, respectively), significantly lower values (lesion number: p < .01; volume: p < .04) were observed for infratentorial lesions, while significantly higher values were seen for cortical/subcortical lesions (lesion number: p < .01; volume: p < .02). A higher lesion/white matter contrast (p < .002), a significant time saving for lesion burden quantitation (p < .05) and very low interobserver variability were found in favor of fast-FLAIR. Our data suggest that, despite the limitations regarding infratentorial lesions, fast-FLAIR sequences are indicated in MS studies because of their good identification of cortical/subcortical lesions, almost complete interobserver agreement, higher contrast-to-noise ratio and the limited time needed for semiautomated quantitation.