We describe changes in apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in tacrolimus associated encephalopathy. ADC was clearly increased and FA decreased in the involved regions. There was a strong local contrast-enhancing effect along the cortical surface. Repeat magnetic resonance imaging five days later showed an increase in FA; but no contrast enhancement. The observed ADC and FA changes in the acute phase suggest that vasogenic edema may play a pivotal role in tacrolimus induced neurotoxicity. The contrast-effect can be explained by disturbed venous drainage caused by thrombotic microangiopathy.