A relatively simple, almost entirely noninvasive imaging-based method is presented for deriving arterial blood input functions for quantitative [(18)F]2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomographic (PET) studies in rodents. It requires only one venous blood sample at the end of the scan. MicroPET images and arterial blood time-activity curves (TACs) were downloaded from the Mouse Quantitation Program database at the University of California, Los Angeles. Three-dimensional regions of interest were drawn around the blood-pool region of the left ventricle and within the liver to derive their respective TACs. To construct the "hybrid" image-derived input function (IDIF), the initial part of the left ventricle TAC, containing the peak concentration of [(18)F]FDG in the arterial blood, was corrected for spillout (ie, partial-volume effect yielding a recovery coefficient < 1) and then joined to the liver TAC (normalized to the 60-minute arterial blood sample) immediately after it peaks. To validate our method, the [(18)F]FDG influx constant (K(i)) was estimated using a two-tissue compartment model and compared to estimates of K(i) obtained using measured arterial blood TACs. No significant difference in the K(i) estimates was obtained with the arterial blood input function and our hybrid IDIF. We conclude that the normalized hybrid IDIF can be used in practice to obtain reliable K(i) estimates.