A molecular epidemiology study of Salmonella serotype Enteritidis was carried out by ribotyping performed with a mixture of PstI and SphI (PS ribotyping), and randomly amplified polymorphic DNA (RAPD) typing conducted with the OPB17 primer. A series, including 38 food and 25 water strains, which were epidemiologically unrelated and collected in Spain over 1985-1996, was differentiated into 20 PS ribotypes [discrimination index (DI) = 0.67], RAPD types (DI = 0.28), and by combining both methods into 23 genomic groups (DI = 0.76). With ribotyping data from the strains tested in this and in a previous work, including clinical and reference strains, a similarity dendrogram was traced and the subsequent branches and groupings were correlated with RAPD types, phage types and sources of origin. At a similarity level of 55%, a major cluster (grouping five subclusters and three single branches) and two minor clusters were revealed. Results supported the fact that organisms representing, at least, 40 genomic groups are currently circulating in Spain, but that only the organisms of five groups predominate and these fall into a single subcluster or lineage. Organisms of these five groups could be considered endemic, associated with food-borne human infections and, for epidemiological purposes, can be differentiated by phage typing. The most frequent phage types can be subdivided into genomic groups. Organisms of the prevalent genomic groups and several less frequent ones were mainly associated with poultry transmission and gastroenteritis as the major clinical forms, while organisms of another two frequent groups were mainly associated with extra-intestinal infections, and organisms of four infrequent groups were only collected from sewage or environmental waters.