In previous studies, we mapped glomerular layer 2-deoxyglucose uptake evoked by hundreds of both systematically related and chemically distinct odorants in rat olfactory bulbs. To determine which principles of chemotopic organization revealed in these studies may be more fundamental and which may be more species typical, we now have characterized patterns of responses to 30 of these odorants in mice. We found that only a few odorants evoked their multiple foci of peak activity in exactly the same locations in the two species. In mice, as in rats, odorants that shared molecular features evoked overlapping patterns, but the locations of the feature-responsive domains often differed in rats and mice. In rats, increasing carbon number within a homologous series of aliphatic odorants is generally associated with rostral and ventral progressions of activity within domains responding to odorant functional group and/or hydrocarbon backbone. Such chemotopic progressions were not obvious in mice, which instead showed more abrupt differences in activated glomeruli within the domains for odorants differing by a single methylene group. Despite the differences, quantitative relationships between overall uptake patterns exhibited a similar organization with respect to odorant chemistry for the two species, probably as a result of partial overlaps of peak domains and more extensive overlaps in large, low-activity areas for rats and mice. We conclude that clustering responses to shared odorant features may be a general strategy for odor coding but that the specific locations of high-activity domains may be unique to a species. J. Comp. Neurol. 514:658–673, 2009. © 2009 Wiley-Liss, Inc.