Existing approaches to characterizing quantitative trait loci (QTL) utilize a paradigm explicitly focused on the direct effects of genes, where phenotypic variation among individuals is mapped onto genetic variation of those individuals. For many characters, however, the genotype of the mother via its maternal effect accounts for a considerable portion of the genetically based variation in progeny phenotypes. Thus the focus on direct effect QTL may result in an insufficient or misleading characterization of genetic architecture due to the omission of the potentially important source of genetic variance contributed by maternal effects. We analyze the relative contribution of direct and maternal effect (ME) QTL to early growth in mice using a three-generation intercross of the Small (SM/J) and Large (LG/J) inbred mouse lineages. Using interval mapping and composite interval mapping, direct effect (DE) QTL for early growth (change in body mass during the interval from week 1 to 2) were detected in the F(2) generation of the intercross (n = 510), where no maternal genetic effect variance is present (all individuals are progeny of genetically identical F(1) mothers). ME QTL were detected by treating the phenotypes of cross-fostered F(3) pups as a characteristic of their nurse-dam (n = 168 dams with cross-fostered progeny). Five DE QTL, significant at a chromosome wide level (alpha = 0.05), were detected, with two significant at a genome wide level. FourME QTL significant at the chromosome wide level were detected, with three significant at the genome wide level. A model containing only DE QTL accounted for 11.8% of phenotypic variance, while a model containing only ME QTL accounted for 31.5% of the among litter variance in growth. There was no evidence for pleiotropy of DE and ME loci since there was no overlap between loci detected in these two analyses. Epistasis between all pairs of loci was analyzed for both DEs and MEs. Ten pairs of loci showed significant epistasis for MEs (alpha = 0.05 corrected for multiple comparisons) while four pairs showed significant epistasis for DEs on early growth.