Nifurtimox (NFX), a compound with known antiprotozoal activity, was evaluated for potential use in the prevention or treatment of histomoniasis in turkeys. A test of NFX in vitro showed that the compound was progressively active at concentrations of 12.5–200 ppm. Lower concentrations appeared only to delay growth of histomonads, while a concentration of 200 ppm was completely inhibitory. A series of tests in turkey poults showed that NFX had significant (P < 0.05) efficacy at 300–400 ppm when given in the feed throughout a 14-day experimental infection period. The beneficial effect was most prominent in the reduction of mortality and the suppression of liver lesions. Cecal lesions appeared less affected. Treatment with 400 ppm for a 3-day period after inoculation of turkeys was partially effective. In all tests, liver lesions were suppressed more effectively than cecal lesions, indicating that the concentration of the compound in the liver during metabolic excretion was important in the observed efficacy of this compound. Lack of any effect on growth or feed consumption in uninfected turkeys during a medication period of 16 days indicated that this compound was well tolerated by turkeys at 400 ppm in the feed and might be of benefit in the prevention or treatment of histomoniasis in turkeys.