The members of a given species display a normal distribution of gene expression which is here termed the species gene ensemble. This more specific designation of the ‘genetic background’ leads to a consideration of why gene targeting outcomes are regulated by the species gene ensemble. One consequence is the utility of the heterozygous knockout which buffers the drastic compensatory reactions of the homozygous knockout thereby revealing subtle but yet consistent alterations in hippocampally-dependent behaviors. Hippocampus 2002;12:105–108. © 2002 Wiley-Liss, Inc.