We began these experiments as an attempt to replicate in the mouse the induction by kainate (KA) of F1/GAP-43 mRNA we observed in adult rat hippocampal granule cells [Mol. Brain Res., 33 (1995) 22-28]. However, even though KA induced behavioral seizures in the mouse similar to those in the rat, neither induction of F1/GAP-43 mRNA nor subsequent mossy fiber sprouting observed in the rat was detected in three different mouse strains. It was also surprising that the distribution of constitutive levels of F1/GAP-43 mRNA in mouse and rat hippocampus was qualitatively different. Indeed, F1/GAP-43 expression in CA3 pyramidal cells was significantly greater in rat than mouse, while F1/GAP-43 expression in CA1 cells of rat and mouse was equivalent using densitometric analysis. Thus, F1/GAP-43 expression in rat is quantitatively higher in CA3 and CA1 pyramidal cells. In mouse, expression was equivalent in these two subfields. In a transgenic mouse bearing a rat F1/GAP-43 promoter-reporter (lacZ) construct (line 252), in-vivo promoter activity of F1/GAP-43 was studied in hippocampal cells. Transgene expression in hippocampal pyramidal subfields, high in CA3, low in CA1 pyramidal cells, paralleled the distribution of rat F1/GAP-43 mRNA levels, not mouse. Differences in the constitutive F1/GAP-43 expression pattern in hippocampus between rat and mouse may therefore be determined by different recognition elements present on the F1/GAP-43 promoter. KA injected into the line 252 transgenic mouse did not activate the rat F1/GAP-43 promoter in mouse hippocampal granule cells. The absence of both F1/GAP-43 mRNA expression induction and promoter activation in mouse granule cells after KA is likely related to genera differences in transcriptional regulatory mechanisms, though post-transcriptional mechanisms cannot be excluded. Since the different hippocampal chemistry of F1/GAP-43 in rat and mouse likely extends to other molecular species, behaviors in rat and mouse that depend on hippocampal function might be different as well. We therefore evaluated spatial memory ability in a delayed matching-to-sample task. In contrast to rat, we were surprised to find no evidence of the ability to learn this task in three different mouse strains. Since interest in mouse genetics in relation to behavior and memory functions of hippocampus is growing, generalizations concerning hippocampal function from studies carried out on the mouse need to be made with caution considering the specific behavioral, pharmacological, and general molecular differences observed here. One can also be opportunistic and exploit the natural variations between these two genera to gain insight into the molecular mechanisms underlying information storage.