Forty-seven isolates, identified morphologically as Giardia duodenalis, were compared by restriction endonuclease analysis of DNA with hybridization to a non-radiolabeled probe. Seven schizodemes were distinguished, compared to 15 zymodemes identified by isoenzyme electrophoresis. Despite the greater sensitivity of isoenzyme electrophoresis, DNA analysis did detect previously unsuspected variations between isolates in 1 zymodeme. Eighteen different genetic groups were detected among the 49 isolates by isoenzyme and DNA analyses. Genetic differences between groups, calculated from DNA restriction fragment variation, were significantly correlated with differences calculated from allozyme variation. This correlation between the 2 techniques suggests that G. duodenalis consists of a complex of genetically diverse clones. Such a genetic structure has important implications for the taxonomy of Giardia and the epidemiology of giardiasis.