The aim was to evaluate the performance of selected individual major histocompatibility complex (MHC) class I and class II alleles and combinations of these on disease resistance against furunculosis. The material, consisting of 2,145 Atlantic salmon (Salmo salar) from seven families, contained four MHC class I (UBA) alleles and two MHC class II alpha (DAA) alleles. The included alleles were previously shown to influence resistance towards furunculosis. The fish were challenged with the bacterium Aeromonas salmonicidae, causing furunculosis. The total mortality in the material was 84.0%, and both dead and surviving fish were genotyped for UBA and DAA. For MHC class II fish with DAA*0301 were more resistant than fish with DAA*0201, which were significantly more susceptible (P < 0.05). For MHC class I, the ranking of performance of the alleles differed from previous results, and fish with allele UBA*0601 were found to be most resistant while fish with UBA*0501, UBA*0201 and UBA*0301 were more susceptible. The analysis of combined MHC class I and class II genotype detected that fish with genotypes UBA*0501/*0501;DAA*0301/*0301, UBA*0601/*0601;DAA*0301/*0301 and UBA*0601/*0601;DAA*0201/*0201 were most resistant (P < 0.05), while the genotypes associated with increased susceptibility were UBA*0501/*0501; DAA*0201/*0301 and UBA*0501/*0501;DAA*0201/*0201 (P < 0.05). In addition, Cox regression analysis show that both family and MHC alleles contributed significantly to survival. Thus, in addition to reproducing the effect on resistance and susceptibility of many MHC class I and class II alleles individually, we also detected an effect of certain MHC class I and class II combinations suggestive of cross-talk between the class I and class II pathways.