The profile of activity across rat somatosensory cortex on stimulation of a single whisker was examined using both intrinsic signal imaging and electrophysiological recording. In the same animals, under sodium pentobarbital anesthesia, the intrinsic signal response to a 5-Hz stimulation of whisker C2 was recorded through a thinned skull. Subsequently, the thinned skull was removed, and individual cortical neurons were recorded at multiple locations and in all cortical layers in response to the same whisker stimulation paradigm. The amplitude of the evoked response obtained with both techniques was quantified across the cortical surface with respect to distance (less than or equal to1.6 mm) from the peak intrinsic signal activity. Cortical neurons were rated as having a significant or nonsignificant whisker-evoked response as compared with a baseline period of spontaneous firing; a minority of neurons exhibited a small but significant increase in neuronal spiking even at long distances (>1.6 mm) from the optically determined peak of activity. Overall, this analysis shows a significant correlation between the two techniques in terms of the profile of evoked activity across the cortical surface. Furthermore, this data set affords a detailed and quantitative comparison between the two activity-dependent techniques-one measuring an intrinsic decrease in light reflectance based largely on metabolic changes and one measuring neuronal firing patterns. Studies such as this, comparing directly between imaging and detailed electrophysiology, may influence the interpretation of the extent of the activated area as assessed with in vivo functional imaging techniques.