Until now, there has been no reliable means of predicting tumor response to chemotherapy in patients with metastatic colorectal cancer. Using arterial nuclide flow scans as a determinant of tumor response, the degree of tumor perfusion was evaluated in a blinded prospective study. Seventy-three patients with colorectal hepatic metastases received continuous hepatic arterial (N = 52) or systemic intravenous (N = 21) chemotherapy using an implantable pump. All patients had pretreatment hepatic arteriography and arterial flow scans using 99mTc macroaggregated albumin (99mTc-MAA). An arteriogram was characterized as positive if it showed tumor hypervascularity; the 99mTc-MAA flow scan was considered positive if it showed increased tumor uptake relative to the liver. Of 47 patients with an evaluable 99mTc-MAA flow scan who were treated with arterial infusion, 31 had a positive scan; in this group 16 responded to chemotherapy. The 99mTc-MAA scan was negative in 16 patients, of whom one responded to chemotherapy (p less than 0.006). The 99mTc-MAA scan had the greatest predictive value in previously untreated patients (sensitivity = 91%; specificity = 77%). The arteriogram was positive in 25 of 46 evaluable patients, but this finding had little predictive value for tumor response (sensitivity = 56%; specificity = 46%). Of 21 patients receiving systemic intravenous infusion, the scan was positive in nine patients, of whom seven responded to chemotherapy. The 99mTc-MAA scan was negative in 12 patients, of whom one responded to chemotherapy (sensitivity = 88%; specificity = 85%). When 99mTc-MAA-positive and -negative groups were compared, there were no differences in mean patient age, per cent liver involvement, tumor size, or plasma liver function tests. Hepatic tumor perfusion as determined by MAA arterial flow scan is a reliable predictor of tumor response in patients with metastases from large bowel cancer. The test provides a valuable criterion for selecting individuals for treatment of metastases from large bowel cancer by infusion chemotherapy.