Marker-quantitative trait locus (QTL) linkage was evaluated in F2 intercross and backcross mouse populations derived from stocks differing dramatically in prolificacy and mature weight. A highly prolific outbred Quackenbush-Swiss mouse line, or an inbred line derived from it (16.62 +/- 0.22 and 14.64 +/- 0.27 pups per litter, respectively) were used as one of the grandparents in these populations. The less prolific C57BL/6J inbred mouse line (6.67 +/- 0.37 pups per litter) was used as the other grandparent. Linkage was evaluated in a three-step process that involved selective genotyping of F2 intercross progeny representing extremes for prolificacy, genotyping of the full F2 for chromosomal regions potentially associated with prolificacy, and genotyping of the backcross for genomic regions significantly associated with prolificacy in the F2. Segments of Chromosomes (Chrs) 2 and 4 were significantly (P < 0.05, experiment-wise error rate) associated with prolificacy, and LOD scores suggestive of linkage were observed for litter size on Chr 9 and growth on Chrs 4 and 11. Existence of growth QTL was also supported by marker effects that were significant (P < 0.05) or approaching significance (P < 0.10) in the backcross. Additive litter size QTL effects ranged from 0.56 to 0.79 pups per litter, and dominance deviations ranged from -0.56 to 1.19 pups per litter, suggesting overdominance as a possible mode of gene action in some cases. The observation of pleiotropic or linked QTL for growth and prolificacy corresponds well with results from many selection experiments identifying positively correlated responses to selection for these two traits.