MRI is the most powerful imaging technique in managing patients with suspected or confirmed multiple sclerosis (MS). However, conventional MRI variables show nonspecific abnormalities weakly correlated with clinical progression of the disease. New techniques, now routinely available, offer better characterisation of the pathophysiology. We combined conventional MRI, including lesion load, contrast enhancement and "black holes" with magnetisation transfer and diffusion-weighted imaging and localised proton MR spectroscopy (MRS) to study their relationship with disability, course and duration of MS. The variables that were the most significantly linked to the course of the disease (relapsing remitting versus secondary progressive) were lesion load, mean overall magnetisation transfer ratio and apparent diffusion coefficient (MGADC), the percentage of ADC in (PADCIMD), and out of (PAD-COMD) modal distribution, and the ratio N-acetylaspartate and creatine-containing compounds on MRS of the centrum semiovale. MGADC and PADCIMD were the independent factors most related to disability and duration of disease. Combining MRI techniques is clinically relevant and feasible for studies of MS and may be applied to other diseases of the central nervous system.