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Histomonas meleagridis, a flagellated protozoan that causes histomoniasis or blackhead disease, is a great threat to the turkey industry with its heavy mortality and morbidity. In vivo studies using H. meleagridis isolated from 3 strains collected from outbreaks in North Carolina (Strain MNC), Michigan (Strain ZM) and Georgia (strain BG) and monocultures generated from the Buford isolate show that each isolate and monoculture varied in virulence. These results suggest the variation in the virulence may contribute to the severity of the blackhead outbreak. Currently, nitarsone (4-nitrophenylarsonic acid) is the only approved drug available in the United States for prevention of histomoniasis. Recent blackhead disease outbreaks in turkeys fed with nitarsone contained feed suggest the possibility of drug resistance in certain strains of the parasites. We tested the sensitivity of MNC, ZM and BG strains to nitarsone using both an in vitro cell culture model and in turkeys. These studies reveal that strain MNC has reduced sensitivity to the nitarsone.