Limbic P300 potentials can be recorded within the mesial temporal lobes of patients with temporal lobe epilepsy (TLE). To delineate possible mechanisms of their generation and pathological alteration, we analysed limbic P300s in 55 TLE patients with and 29 without Ammon's horn sclerosis (AHS) and correlated their amplitudes with neuronal cell counts in 30 histopathological specimens. Limbic P300 amplitudes were reduced on the side of the epileptogenic focus only in patients with AHS. Moreover, in AHS patients, limbic P300 latencies were prolonged bilaterally; and in patients with left-sided AHS, amplitudes were reduced bilaterally. Both findings suggest bilateral functional deficits in TLE with unilateral AHS. Limbic P300 areas correlated significantly with neuronal densities of dentate gyrus granule cells but not hippocampal pyramidal cells in the CA1–4 (cornu ammonis) subfields. This finding points to a potential mechanism for the bilateral effects of unilateral AHS as both dentate gyri exhibit strong reciprocal contralateral connectivity.