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Melanocortin 4 receptor (MC4R) is expressed in the appetite-regulating areas of the brain where it is central in the regulation of feed intake and energy balance. A mutation in MC4R causing an Asp298Asn substitution has been associated with fatness, high daily gain and feed intake in the pig. In a previously performed genome scan based on a Hampshire × Landrace cross, we detected one quantitative trait loci (QTL) affecting carcass fat/meat ratio and one QTL affecting the biceps femoris muscle, both close to the position of MC4R on porcine chromosome 1. In this study, the two lines were found to be close to fixation for alternative alleles of the Asp298Asn polymorphism. Additional QTL analyses supported our hypothesis of MC4R as a positional candidate gene but only for the fat/meat QTL. The Asp298Asn polymorphism was also evaluated as a selection target for daily gain in a Danish pig breeding population that included four breeds (Hampshire, Duroc, Landrace and Yorkshire). Over a 12-year period (1990–2002), a significant increase in the allele frequency of 298Asn was found in Landrace and Duroc, whereas a non-significant decrease in the 298Asn allele frequency was observed in Yorkshire. The Hampshire breed was fixed for the 298Asn allele in 1990. The high 298Asn allele frequencies in Hampshire, Landrace and Duroc are most likely due to selection for daily gain, whereas selection for daily gain in the Yorkshire breed apparently focuses on other loci.