The development of Sarcocystis cruzi was compared in 3- to 14-day-old calves (n = 38) inoculated with 55,000 to 500,000,000 sporocysts from intestinal scrapings of coyotes, and euthanatized and necropsied on postinoculation days (PID) 4 to 153. From PID 15 to 19, the calves remained clinically normal, except for fever (greater than or equal to 40 C), during the development of 1st-generation meronts, and lesions in calves euthanatized at this time were confined mainly to mesenteric lymph nodes and consisted of focal necrosis due to vascular thrombosis. On PID 26, calves became sick, coincident with maturation and rupture of 2nd-generation meronts. In calves euthanatized from PID 26 to 28, the main lesion was hemorrhage in many organs and 1st- and 2nd-generation meronts were located subendothelially in unidentified cells between endothelium and tunica elastica. In calves euthanatized on PID 31, inflammation was pronounced in many tissues; this was also seen in calves euthanatized from PID 31 to 46 and corresponded to individual merozoites and the early development of sarcocysts. Inflammation began to subside by the time sarcocysts were recognizable (PID 67). Nonsuppurative hepatitis occurred in calves euthanatized from PID 15 to 153.