The purposes of this study were to determine whether the pretreatment apparent diffusion coefficients (ADCs) of hepatic metastatic lesions from colorectal cancer are predictive of response to chemotherapy and to compare the ADCs of metastatic lesions before and after chemotherapy. Twenty patients with potentially operable hepatic lesions larger than 1 cm in diameter metastatic from colorectal carcinoma were prospectively evaluated with diffusion-weighted imaging at three b values before and after chemotherapy. Quantitative ADC maps were calculated with images with b values of 0, 150, and 500 s/mm2 (ADC0-500) and with images with b values of 150 and 500 s/mm2 (ADC150-500). Regions of interest were drawn around metastatic lesions and randomly over liver. The mean ADC0-500 and mean ADC150-500 of metastatic lesions before and after chemotherapy were compared according to response defined by Response Evaluation Criteria in Solid Tumors criteria. Twenty-five responding and 15 nonresponding metastatic lesions were evaluated. Nonresponding lesions had a significantly higher pretreatment mean ADC0-500 and mean ADC150-500 than did responding lesions (Mann-Whitney U test, p < 0.002). There was a linear regression relation (r2 = 0.34, p = 0.02) between percentage size reduction of metastatic lesions and pretreatment mean ADC150-500. After chemotherapy, responding lesions had a significant increase in mean ADC0-500 and ADC150-500 (Wilcoxon's signed rank, p = 0.025). No significant change was observed in nonresponding metastatic lesions (Wilcoxon's signed rank, p > 0.5) or in normal liver parenchyma (Wilcoxon's signed rank, p > 0.4). High pretreatment mean ADC0-500 and mean ADC150-500 of colorectal hepatic metastatic lesions were predictive of poor response to chemotherapy. A significant increase in mean ADC0-500 and ADC150-500 was observed in metastatic lesions that responded to chemotherapy. These findings may have implications for development of individualized therapy.