Human recombinant interferon-alpha-2b (IFN) is known to inhibit growth of both normal and tumor cells and to stimulate immune effector cell function. We have previously shown that IFN and other biological response modifiers augment accumulation of radiolabeled antibodies in tumors. This investigation demonstrates that 30 min post i.m. administration of IFN significantly (p < 0.01) enhances tumor perfusion in tumor-bearing mice and persists for a much longer time than in normal tissue, which, in part, may contribute to the enhanced tumor uptake of radiolabeled monoclonal antibodies within 1.5 h of their administration. Histological examinations of tumors obtained from animals receiving IFN 72 h previously did not show changes in inflammatory cells. Our investigation shows that laser Doppler flowmetry and color Doppler imaging can provide an excellent means of measuring tumor perfusion changes in small living animals where radioactive tracers cannot be used.