Enhancement of lesions in multiple sclerosis (MS) has been investigated using standard and high doses of gadolinium. The purposes of this study are to compare the relative merits of single and triple dose as well as examine the merits of delayed triple-dose images in a large group of patients. Thirty-seven patients with multiple sclerosis underwent contrast enhanced brain magnetic resonance imaging (MRI). After noncontrast images, a single dose (0.1 mmol/kg) of gadoteridol was administered. Subsequently, axial T1-weighted images were obtained immediately after administration, and again after a delay of approximately 20 minutes. After an additional 0.2-mmol/kg dose was administered, to provide a total cumulative dose of 0.3 mmol/kg of gadoteridol, immediate and delayed axial T1-weighted image sequences were repeated. The contrast-noise ratio (C/N) was calculated for each identified, enhancing lesion in each series. Furthermore, blinded readings were performed to determine the lesion detection rate. Of the forty definite lesions that underwent all four sequences, triple-dose delayed images exhibited the highest contrast-noise ratio in a significantly larger number of lesions (p < 0.0001). Triple-dose immediate and delayed scans resulted in significantly higher contrast-noise ratios (6.47 and 9.99, respectively) when compared with those of the single dose scans (3.4 for immediate scans and 5.24 for delayed) (p < 0.01). The lesion detection rate was highest for triple dose delayed (95%), followed by triple-dose immediate (83%), single-dose delayed (68%) and finally, single-dose immediate scans (43%). Triple-dose immediate was noted to have a significantly increased (p < 0.0002) lesion detection rate with respect to the standard-dose immediate scans and standard-dose delayed scans (p < 0.02). In four lesions (10% of the total number of lesions), detection occurred only with the triple-dose delayed image sequence. Triple-dose 0.3 mmol/kg gadolinium with delayed imaging resulted in the highest lesion conspicuity and the highest lesion identification rate. There was a trend of progressively increasing detection rates from single-dose immediate scans to triple-dose delayed scans. Triple-dose delayed scans resulted in significantly higher (p < 2 x 10(-8) contrast noise ratios than all other sequences of this study.