Demonstration of focal alterations of brain metabolism with positron emission tomography has become a widely used method for identifying epileptic foci. Here we investigated how neuronal and glial cell activity relates to alterations of brain metabolism. Acutely induced epileptic activity in the motor cortex of rat brain increased metabolism in the focus and homotopic contralateral areas, and decreased metabolism in the ipsilateral somatosensory area. Increases and decreases of deoxyglucose uptake did not directly correlate with excitations and inhibitions; instead, deoxyglucose uptake was related to the overall strength of synaptic activity, and both strong excitations and strong inhibitions increased brain metabolism. Reduction of metabolism below normal values was associated with reduced synaptic activity and with tonic hyperpolarization of the cells. Our results show that in the absence of structural abnormalities, hypometabolism indicates functional disturbances which may be both reversible and remote from the epileptogenic focus.