Phylogenetic relationships among 19 extant species of rodents, with special emphasis on rats, mice, and allied Muroidea, were studied using sequences of the nuclear protein-coding gene LCAT (lecithin:cholesterol acyltransferase), an enzyme of cholesterol metabolism. Analysis of 705 base pairs from the exonic regions of LCAT confirmed known groupings in and around Muroidea. Strong support was found for the families Sciuridae (squirrel and marmot) and Gliridae (dormice) and for suprafamilial taxa Muroidea and Caviomorpha (guinea pig and allies). Within Muroidea, the first branching leads to the fossorial mole rats Spalacinae and bamboo rats Rhizomyinae. The other Muroidea appear as a polytomy from which are issued Gerbillinae (gerbils), Murinae (rats and mice), Sigmodontinae (New World cricetids), Cricetinae (hamsters), and Arvicolinae (voles). Evidence from LCAT sequences agrees with that from a number of previous molecular and morphological studies, both concerning branching orders inside Muroidea and the bush-like radiation of rodent suprafamilial taxa (caviomorphs, sciurids, glirids, muroids), thus suggesting that this nuclear gene is an appropriate candidate for addressing questions of rodents relationships.