Early ischemic change after stroke can be demonstrated with diffusion-weighted imaging (DWI) and quantified by measuring the apparent diffusion coefficient (ADC) and/or lesion volume. We examined the reliability and reproducibility of lesion volume and ADC measurement on DWI images, and discuss the implications for clinical studies. Using 38 DWI scans from 15 stroke patients, two observers (a physicist and a neuroscience graduate) blind to each other, recorded the lesion volume on DWI sequences, measured the ADC values in this volume and calculated the ratio of ischemic: control ADC (ADCr). One observer repeated his measurements blind to his first, and also examined the effect on lesion volume and ADC of deliberately varying by only one pixel, the outline of the visible boundary of the lesion. The inter and intra-rater reliability were worse for lesion volume than ADC or ADCr measurements: lesion volume, inter-rater coefficient of variation (CoV) 85 +/- 130%, intra-rater CoV 20+/-SD80% (p < 0.05); ADC inter-rater CoV 7.7 +/- SD 19%, intra-rater CoV 0.2 +/- SD 12% (p = NS); and ADCr inter-rater CoV 8 +/- SD27%, intra-rater CoV 0.8 +/- SD73% (p = NS). Altering the position of the outline tracing of the lesion boundary by one pixel altered the measured volumes by 22 +/- SD25% (p < 0.05), but ADC values were altered by only 2.9 +/- SD4.9% and ADCr by 2.7 +/- SD4.8% (p = NS). ADC and ADCr values are more reliable and reproducible than DWI lesion size in acute ischemic stroke because altering where the lesion boundary is measured has a much greater impact on lesion volume than on the ADC or ADCr. This effect is greatest in large lesions. (C) 2003 Elsevier Inc. All rights reserved.