Interferon (IFN) upregulates tumor antigenic expression and enhances tumor uptake of radiolabeled tumor-specific monoclonal antibody (MAb). IFN also increases tumor blood flow. The relationship between these phenomena was investigated. Human melanoma tumors grown in nude mice were used as the experimental tumor model, and 99mTc-MEM136 as an MAb. Tumor blood flow was monitored by ultrasound Color Doppler Imaging (CDI) and Laser Doppler Flowmetry (LDF) techniques. Tumor blood flow increased at 20 min after administration of IFN. Enhancement lasted for about 60 min before the blood flow returned to the original baseline level. Tissue distribution of 99mTc-MEM136 was studied under different experimental schemes. Tumor uptake of 99mTc-MEM136 enhanced significantly only in experimental scheme A (5.5 +/- 0.2% ID/g vs. 3.0 +/- 0.9% ID/g in control group, p = 0.04). In this scheme IFN was given 30 min prior to the administration of 99mTc-MEM136, and the animals were sacrificed 1.5 h later. No upregulation of anti-genic expression was reported at this time. The increased tumor uptake at this early period appeared to be the result of enhanced tumor blood flow.