Experimental epileptic models have been developed to assess the pathophysiology of epileptic seizures. We have previously shown that epileptic seizures cause significant neuronal loss in hippocampus (p<0.05). This study was undertaken to estimate the volume of rat hippocampus stratum pyramidalis in a penicillin-induced epilepsy model, using a stereological method, i.e., "Cavalieri method". Either 500 IU penicillin-G in 0.1 ml or the same volume of saline was administered intracortically. A week later, animals were decapitated, their brains were removed by craniotomy, frozen and cut at a thickness of 150 mum in a cryostat. Sections were stained with hematoxylin-eosin. The total and individual volumes of stratum pyramidalis layer of CA1, CA2 and CA3 subfields of hippocampus were then estimated. Results showed that unlike the decrease in the number of hippocampal neurons, the decrease in the total volume of hippocampus in experimental group of rats (4.55 +/- 0.31 mm(3)) was not statistically significant compared to that of control group of rats (4.67 +/- 0.25 mm(3); p>0.05). This study suggests that the loss of hippocampal neurons in penicillin-induced epilepsy seizure is not directly correlated with a volume change in the hippocampus. Furthermore, our results indicate that it is important to assess both the neuron number and the volume of the affected area using stereological methods in an epilepsy model to objectively analyze the effects of the seizure.