Hippocampal dentate granule cells in temporal lobe epilepsy (TLE) patients with mesial sclerosis (MTLE) are reported to be hyperexcitable compared to those in patients with a mass lesion outside the hippocampus (MaTLE) (Williamson, Clin Neurosci 1994;2: 47-52). To determine if such hyperexcitability is associated with an altered morphology of these neurons, Lucifer Yellow-filled granule cells from MTLE patients were compared with those from MaTLE. The morphology of granule cells in both subject groups resembles closely that of human granule cells described previously by Golgi studies. About 40% of human granule cells have basal dendrites. Additionally their apical dendrites are much more limited in their spread in the longitudinal axis of the hippocampus contributing perhaps to a much more narrow lamellar organization than in rats. Analysis of variance computed on 21 morphometric parameters reveals a significant increase in the length of the portion of the dendrite in the inner molecular layer (IML), and a decrease in length in the outer third of the molecular layer in MTLE, compared to MaTLE. Factor analysis performed on the morphometric features of each group of neurons reveals that in the MaTLE neurons the most distinctive feature is the total dendritic length and the overall distribution of spines on them, whereas in MTLE a lengthening and elaboration of the dendrites in the IML is most distinctive. Previous observations of increased synaptic terminals containing neuropeptides, and neurotransmitter receptors in the IML taken in conjunction with an elaboration of granule cell dendrites in this region, suggest considerable synaptic reorganization within the IML of the MTLE hippocampus which may contribute to its epileptogenicity.