Transgenic or knockout mouse models provide the opportunity to study the function of disease-related or novel genes. However, a confounding factor in all such research is the genetic and phenotypic variation of the mouse strain used to construct the models. A trait which is frequently studied in transgenic models of neurological disorders is synaptic transmission and plasticity of the dentate gyrus of the hippocampus. Consequently, we have investigated the variation in this trait across five strains of mouse (129 Ola, C3H, C57 albino, DBA/2, and FVB/N), in vivo. 129 Ola mice were found to have significantly larger maximal evoked EPSP slope and population spike amplitudes compared to the other strains. No differences across strains were found in paired-pulse facilitation of EPSP slope, a measure of pre-synaptic short-term plasticity. DBA/2 mice showed significantly reduced paired-pulse inhibition of population spike, a measure of poly-synaptic inhibitory feedback within the dentate gyrus. Potentiation of EPSP and population spike, following tetanic stimulation of the perforant path, was observed in all strains. However, DBA/2 mice showed a deficit in the maintenance of potentiation over 1 h, which confirms a previous report [S. Matsuyama, U. Namgung, A. Routtenberg, Long-term potentiation persistence greater in C57BL/6 than DBA/2 mice: predicted on basis of protein kinase C levels and learning performance, Brain Res. 763 (1997) 127-130]. These results show that electrophysiological traits do vary significantly across mouse strains, and that the selection of the strain may have a significant impact on results. Furthermore, since production of a transgenic or knock-out mouse frequently requires cross-breeding, care should be taken in establishing the contribution of parent strains to the final phenotype, as well as the potential interaction with the phenotype arising from the knock-out or transgene.