Functional neuroimaging signals are generated, in part, by increases in cerebral blood flow (CBF) evoked by mediators, such as nitric oxide and arachidonic acid derivatives that are released in response to increased neurotransmission. However, it is unknown whether the vascular and metabolic responses within a given brain area differ when local neuronal activity is evoked by an activity in the distinct neuronal networks. In this study we assessed, for the first time, the differences in neuronal responses and changes in CBF and oxygen consumption that are evoked after the activation of two different inputs to a single cortical area. We show that, for a given level of glutamatergic synaptic activity, corticocortical and thalamocortical inputs evoked activity in pyramidal cells and different classes of interneurons, and produced different changes in oxygen consumption and CBF. Furthermore, increases in stimulation intensities either turned off or activated additional classes of inhibitory interneurons immunoreactive for different vasoactive molecules, which may contribute to increases in CBF. Our data imply that for a given cortical area, the amplitude of vascular signals will depend critically on the type of input, and that a positive blood oxygen level-dependent (BOLD) signal may be a consequence of the activation of both pyramidal cells and inhibitory interneurons.