After surveying various regions of Ethiopia using clinical examinations, filter paper indirect hemagglutination (IHA) test, and hydatid skin test, a hyperendemic focus of hydatid disease (Echinococcus granulosus) was found in southwestern Ethiopia. Two tribes, the Dassanetch and Nyangatom, in the lower Omo River Valley were found to have a particularly high prevalence of the disease. Of 1,342 individuals from these two tribes 4.8% had palpable abdominal cysts and 15% had hepatomegaly. This contrast with 0.2% and 5.6%. respectively, for all other groups combined. Among the Dassanetch and Nyangatom, 6.4% had filter paper indirect hemagglutination titers of 1:128 or greater versus only 0.3% for the combined results of other tested Ethiopian groups. Of 366 Dassanetch and Nyangatom, 31.7% were positive by the hydatid skin test versus 5.9% for all other southwestern Ethiopian tribes tested. Marked sex differences in hydatid skin test positivity, not reflected in the clinical findings or the IHA results, limit the use of this test for hydatid disease and suggest the possibility that men may be exposed more frequently than women to other antigens crossreacting with the hydatid skin test antigen.