Six groups of six pregnant ewes each were inoculated with 170,000 or 1,700,000 tachyzoites of Neospora caninum on gestation day 65, 90, or 120. All ewes seroconverted, and none showed signs of illness other than abortion. Regardless of the inoculum dose, all ewes inoculated on gestation day 65 aborted; ewes inoculated on gestation day 90 aborted, gave birth to weak lambs, or gave birth to clinically normal lambs; and all ewes inoculated on gestation day 120 gave birth to clinically normal lambs. Using an immunohistological procedure that stains bradyzoites, we observed protozoal cysts in brains of 11 of 29 (38%) aborted fetuses, in one of four (25%) weak lambs, and in seven of 18 (39%) clinically normal lambs. Cysts were not observed in extraneural tissues from two clinically normal lambs that had cysts in the brain. No evidence of infection was observed in tissues of five ewes examined using an immunohistological procedure that stains N. caninum tachyzoites and bradyzoites. Multifocal nonsuppurative encephalitis was observed in 46 of 51 (90%) aborted, weak, or clinically normal lambs. Cerebral necrosis, dystrophic mineralization, and meningitis were also commonly identified in live and aborted lambs (even when severely autolyzed). Nonsuppurative, necrotizing placentitis was observed in 15 of 17 (88%) placentas. Nonsuppurative myositis was common in fetuses but not in live lambs. Inflammation occurred less frequently in liver and lung. Clinical and pathological features of neosporosis in sheep closely resemble those of bovine neosporosis and ovine toxoplasmosis. Although abortion caused by naturally occurring neosporosis in sheep has not been reported, diagnosticians should carefully distinguish between neosporosis and toxoplasmosis in cases of ovine protozoal abortion unless future investigations exclude the likelihood of naturally acquired neosporosis in sheep.