1. There is a long-standing debate about whether the large spiny cells in the hilar region of the hippocampus should be classified as pyramidal cells of Ammon's horn or as a distinct cell type of the dentate gyrus. The rationale for grouping these hilar neurons (termed "mossy cells") with pyramidal cells of Ammon's horn is shared characteristics. In the present study we have compared the morphological and physiological characteristics of mossy cells and nearby CA3c pyramidal cells with the use of a rat hippocampal slice preparation. 2. Biocytin-labeled neurons were examined on the basis of soma area, location, shape, number of primary dendrites, extent of dendritic spines, dendritic location, and axon trajectories. Mossy cells had larger soma areas than CA3c pyramidal cells, and they had more large complex spines (thorny excrescences) on their proximal dendrites and somata than CA3c pyramidal cells. Mossy cell dendritic trees and axon collaterals ramified in different regions of the hippocampus than dendrites and axons of CA3c pyramidal cells. 3. Intrinsic physiological properties, and spontaneous and evoked synaptic properties, were measured and compared. Mossy cells had significantly higher input resistances, smaller amplitude burst afterhyperpolarizations, smaller amplitude action potentials, less spike-frequency adaptation, and more anomalous rectification than CA3c pyramidal cells. 4. Mossy cells had spontaneous excitatory postsynaptic potentials (EPSPs) that were significantly higher in frequency and larger in amplitude than CA3c pyramidal cells. A larger proportion of mossy cells than CA3c pyramidal cells responded to perforant path stimulation with depolarizing postsynaptic potentials without any apparent hyperpolarization. Conversely, a smaller proportion of mossy cells than CA3c pyramidal cells responded to perforant path stimulation with inhibitory postsynaptic potentials (IPSPs), and spontaneous IPSPs were more difficult to detect in mossy cells. 5. The intrinsic physiological properties of mossy cells endow these cells with potent excitatory mechanisms but relatively fewer inhibitory control processes than CA3c pyramidal cells. Recordings of spontaneous and evoked PSPs suggest that mossy cells receive more excitatory input and less inhibitory input than CA3c pyramidal cells. These intrinsic and synaptic properties of mossy cells may explain this cell type's exceptional vulnerability to excitotoxic damage by intense afferent stimulation. 6. In summary, mossy cells were significantly different from CA3c pyramidal cells in many of their morphological, intrinsic physiological, and synaptic properties.(ABSTRACT TRUNCATED AT 400 WORDS)