BACKGROUND AND PURPOSES: New strategies have been developed to improve the sensitivity of contrast-enhanced MR imaging in quantifying disease activity in patients with multiple sclerosis (MS). The goal of the present study was to evaluate the sensitivity of T1-weighted images after injection of a triple dose of contrast material and application of a magnetization transfer (MT) pulse in the detection of enhancing lesions as compared with the conventional approach. METHODS: Monthly MR images were obtained in 13 patients with relapsing-remitting MS for a period of 3 months. The MR studies were performed on two separate occasions with single- and triple-dose contrast material. In each session, T1- and T2-weighted spin-echo images with and without the MT pulse were obtained before and after contrast administration. All images were evaluated in a blinded fashion and scored in random order and consensually by two readers. The number of total and new enhancing lesions and active images was counted. RESULTS: Eighty-six percent more enhancing lesions and 54% more new enhancing lesions were detected with triple-dose as compared with single-dose non-MT sequences, whereas single-dose MT images depicted 33% more enhancing lesions and 18% more new enhancing lesions than the single-dose non-MT images. Twenty-nine percent more lesions were detected on triple-dose non-MT images than on single-dose MT images. The combination of a triple dose of contrast material and MT did not produce any significant change in detection of enhancing lesions as compared with a triple dose of contrast without MT. CONCLUSION: The use of a triple dose of contrast material is the best approach to maximize the sensitivity of enhanced MR imaging. ; This is an article as published in American Journal of Neuroradiology. It is available throught their website at http://www.ajnr.org/cgi/reprint/19/10/1863