Capabilities of diffusion-weighted (DW) and magnetization transfer (MT) imaging are well established for tissue characterization in various pathologies individually. However, the effect of suppression of macromolecules on applying MT pulse on signals associated with DW imaging and resulting change in the apparent diffusion coefficient (ADC) of water molecules has not been demonstrated previously. In the present study, we have performed DW echo planar imaging (EPI) with and without MT preparation pulse to see the effect of macromolecular signal suppression on ADC. A total of 10 normal volunteers and 20 patients with different intracranial cystic lesions [abscesses (n=10), cystic tumors (n=5), arachnoid cysts (n=5)] were subjected to DW imaging (b=0 and 1000 s/mm(2)) with and without MT saturation pulse. Analysis of region of interest (ROI) from different areas of white matter in normal volunteers and in the wall and cavity of cystic lesions in patients was carried out for calculating the ADC values. We found a significant increase (P<.05) in the ADC values in brain parenchyma and cavity of those intracranial cystic lesions having considerable amount of proteins after the application of MT preparation pulse except for arachnoid cysts. This is due to the size of the macromolecules present in the normal and abnormal tissue. Our studies suggest that this technique is likely to give a novel image contrast and may be of value in improving the tissue specificity in pathologies associated with variable macromolecular size.