The purpose of this study was to determine if the apparent diffusion coefficient (ADC) on diffusion-weighted MRI could predict the response of patients with advanced pancreatic cancer to chemotherapy. Diffusion-weighted MRI was performed in 63 consecutive patients with advanced pancreatic cancer who were subsequently treated with chemotherapy. The ADC values of the primary tumour with a middle b-value (400 s mm(-2)) and a high b-value (1000 s mm(-2)) were determined; cystic or necrotic components were avoided. The patients were classified into two groups: (i) those with progressive disease and (ii) those who were stable 3 months and 6 months after initial treatment. The groups were compared with respect to the ADC and clinical factors, including gender, age, Union International Contre le Cancer (UICC ) stage, initial tumour size and chemotherapy agents used. Local tumour progression rates were evaluated using the Kaplan-Meier method. The middle b-value ADC of the pancreatic cancers ranged from 0.93-2.42 x10(-3) mm(2) s(-1) (mean, 1.50 x10(-3) mm(2) s(-1)), and the high b-value ADC ranged from 0.72-1.88 x10(-3) mm(2) s(-1) (mean, 1.20 x10(-3) mm(2) s(-1)). The high b-value ADC was significantly different between the progressive and stable groups at 3 months' and 6 months' follow-up (p = 0.03 and p = 0.04, respectively). The rate of tumour progression was significantly higher in those with a lower high b-value ADC than in those with a higher b-value ADC (median progression time, 140 days vs 182 days; p = 0.01). In conclusion, a lower high b-value ADC in patients with advanced pancreatic cancer may be predictive of early progression in chemotherapy-treated patients.