If ultra-early stratification of radiotherapy response was possible it could potentially reduce unnecessary irradiation of normal tissue and improve disease management. In this study repeated diffusion weighted magnetic resonance imaging was conducted along with fractionated radiotherapy in brain metastases patients. It was found that the decrease in the apparent diffusion coefficient (ADC) observed 24 hours after the first radiotherapy fraction may be an indicator of irradiation. Responding patients versus non-responding patients could be differentiated by their corresponding change in ADC seen 48 hours after start of radiotherapy. These findings may have great impact for the emerging hybrid MR – linear-accelerator systems.