The goal of this study was to test whether clinician-rated regional cerebral blood flow (rCBF) as rendered by SPECT imaging is a meaningful predictor of patient response to CNS stimulants. Chart reviews were used to identify patients who reported prior significant positive and negative responses to CNS stimulants. Each patient in the study had received resting and concentration SPECT scans using Tc99m exametazime. Differences in cerebral blood flow for frontal regions of interest were assessed in three conditions (resting, concentration, and their difference, or "delta") using ANCOVAs and age-matched ANOVAs. Prefrontal pole deltas were found to be highly sensitive and specific predictors of response to CNS stimulants, with pole activation predicting adverse responses and pole deactivation predicting good responses. Positive and negative predictive values were greater than .75 for both poles. We conclude that SPECT renderings of rCBF, particularly in the prefrontal cortex, are a potentially powerful clinical tool for anticipating response to stimulant medications, both positive and adverse.