By using models which incorporate both numerical and gene-frequency dynamics, we investigate the conditions for a stable polymorphism in host disease resistance when there is a genetically uniform pathogen. We show that polymorphism is more likely when the difference in resistance conferred by alternative alleles is large rather than small. This conforms with the frequent observation of major gene effects on resistance. Moreover, when allelic differences in resistance are large, polymorphism is possible over a wide range of costs, including situations where costs approach values close to zero. The actual resistance cost that can be sustained in such polymorphic populations is dependent on the transmission mode and the intensity of disease-independent population regulation. Expectations regarding resistance costs in any particular host-pathogen system will be dependent on knowledge of the epidemiological and genetic characteristics of that system.