Enterotoxigenic Escherichia coli (ETEC) that express the F4ab or F4ac fimbriae (formerly known as K88ab/ac) are major causes of diarrhea and death in neonatal and young pigs. A locus controlling susceptibility towards ETEC F4ab/ac has previously been mapped to pig chromosome 13q41. A number of studies indicate that candidate genes for this trait could either be transferrin-like-genes or mucin-like sialoglycoproteins. Deductions based on linkage and comparative mapping data point to mucin 4 (MUC4) as a likely candidate. Incidentally, the gene lies in one of the candidate regions on Hsap3 (viz., Hsap3q29). We isolated pig BAC clones containing MUC4, and mapped the BACs by FISH to SSC13q41. FISH mapping on interphase nuclei positioned MUC4 between microsatellite markers Sw207 and S0283 while radiation hybrid mapping positioned it between SST and SWR2189. Initial screening for polymorphism in the gene revealed a SNP in intron 7 that shows complete co-segregation with ETEC F4ab/ac susceptibility in a Wild boar/Large White intercross. We report on the genomic characterization of the porcine mucin 4 gene spanning 25 exons and more than 31 kb. Comparison between the porcine mucin 4 gene and the human ortholog shows conservation between 58% and 89% on the nucleotide level of the different exons. Highly conserved non-protein coding sequences are also evident from the comparison. Alignment between porcine and murine MUC4 shows less conservation than the pig-human comparison. In addition to the genomic sequence of pig mucin 4 we also report on more than 15 SNPs discovered in the porcine MUC4 sequence. Collaboration with the Danish Slaughterhouses on genotyping of the intron 7 SNP of Mucin 4 in 6.373 breeding boars (3.432 Landrace and 2.941 Large White) and analysis of their offspring has revealed data of relevance to neonatal survival. Analysis on offspring from 6.373 animals show a highly significant (P < 0.0001 for Landrace and P = 0.0003 for Large White) positive correlation between the R-allele and living piglets on day five after birth, whereas there is a negative correlation to meat content, but all in all the more R-alleles the better breeding value in the current Danish breeding scheme.