Detecting some of the genes that influence disease resistance would improve our understanding of the processes that cause disease and also simplify disease control. Genes within the major histocompatibility complex (mhc) are strong candidates for disease resistance and they have been intensely studied for the last 30 years. Recently, several groups working independently have reported the existence of alleles within the mhc that are associated with enhanced resistance to nematode infection. This article uses hindsight to describe some of the potential pitfalls that hinder the search for valid disease resistance genes. The search requires a good understanding of disease biology, molecular genetics, statistical genetics and especially, the design and analysis of experiments. The power to detect mhc effects is quite low and is quite sensitive to the frequency of the putative resistance alleles.