Polymorphism at the estrogen receptor locus (ESR) and its association with reproductive performance in Landrace pig is reported. A total of 124 sows from a control line, and 163 sows from a line selected for litter size were genotyped. The traits studied were number born alive (NBA) and total number born (TNB). Prolificacy in first, second and third or later parities were considered as three different traits. A mixed model considering the ESR genotype as a fixed effect and polygenic background as a random effect, was carried out using Bayesian inference, implemented via the Gibbs sampling procedure. Two alternative statistical models, with and without ESR genotype by line interaction, were considered. Association of an additive ESR effect with NBA and TNB was not detected. Moreover, in third and further parities, a line by ESR genotype interaction was observed for both NBA and TNB. For third and further parities, allele B was associated with increasing litter size in selected animals, whereas the opposite was observed in control animals. These results suggest that a background genotype by ESR interaction exists, although a spurious association due to sampling or the possibility of different linkage phases between the ESR polymorphism and a putative QTL close by cannot be ruled out.