According to the theory of mate choice based on heterozygosity, mates should choose each other in order to increase the heterozygosity of their offspring. In this study, we tested the ‘good genes as heterozygosity’ hypothesis of mate choice by documenting the mating patterns of wild Atlantic salmon (Salmo salar) using both major histocompatibility complex (MHC) and microsatellite loci. Specifically, we tested the null hypotheses that mate choice in Atlantic salmon is not dependent on the relatedness between potential partners or on the MHC similarity between mates. Three parameters were assessed: (i) the number of shared alleles between partners (x and y) at the MHC (Mxy), (ii) the MHC amino–acid genotypic distance between mates' genotypes (AAxy), and (iii) genetic relatedness between mates (rxy). We found that Atlantic salmon choose their mates in order to increase the heterozygosity of their offspring at the MHC and, more specifically, at the peptide–binding region, presumably in order to provide them with better defence against parasites and pathogens. This was supported by a significant difference between the observed and expected AAxy (p = 0.0486). Furthermore, mate choice was not a mechanism of overall inbreeding avoidance as genetic relatedness supported a random mating scheme (p = 0.445). This study provides the first evidence that MHC genes influence mate choice in fish.