Halofuginone was evaluated for its activity against experimentally induced infection due to Cryptosporidium parvum in rats rendered immunosuppressed with dexamethasone. The drug's activity was dose-related and both prophylaxis and therapy reduced the rate and severity of infection in the small intestine and caecum. Prophylactic treatment reduced infection of the common bile duct, but therapeutic administration did not and neither form of treatment reduced the infection rate in the colon. Intestinal infection recurred at a level comparable to that of untreated controls when treatment was discontinued. Treatment with halofuginone may reduce the severity of acute cryptosporidiosis, but is less efficacious for chronic cryptosporidiosis involving the colon and extraintestinal tissues, a manifestation increasingly seen in the immunocompromised host.