Phenotypic and histological responses of cultivated lettuce (Lactuca sativa) and wild relatives L. saligna, L. virosa as well as interspecific crosses derived from L. sativa × L. serriola to two races of Bremia lactucae (CS2, CS9) were investigated. With the exception of L. sativa genotypes, all accessions and hybrids expressed incomplete or complete resistance to both pathogen races, with slight differences at seedling and adult plant stages, respectively. Histological features of the interactions (development of pathogen infection structures and host hypersensitive response to attempted infection) were studied on leaf discs 48 h after inoculation. Interactions with similar phenotypic expression of resistance were characterized by significant variation in rate of development of pathogen infection structures and hypersensitive reactions. Differences found within eight Lactuca spp. accessions and hybrids challenged by two distinct pathogen races are interpreted and discussed.