Change-distribution analysis and intersubject averaging of subtracted positron emission tomography (PET) images are new techniques for detecting, localizing, and quantifying state-dependent focal transients in neuronal activity. We previously described their application to cerebral blood flow images (intravenous bolus H215O, Kety autoradiographic model). We now describe their application to images of H215O regional tissue activity without conversion to units of blood flow. The sensitivity and specificity of response detection and the accuracy of response localization were virtually identical for the two types of images. Response magnitude expressed in percent change from rest was slightly, but consistently smaller in tissue-activity images. Response magnitude expressed in z-score was the same for the two-image types. Most research and clinical applications of functional brain mapping can employ images of H215O tissue activity (intravenous bolus, 40-sec nondynamic scan) without conversion to units of blood flow. This eliminates arterial blood sampling, thereby simplifying and minimizing the invasivity of the PET procedure.