Cryptosporidium is leading cause of calf morbidity and mortality due to diarrhea on dairy farms in North America, and is the second leading cause of diarrhea in infants in developing countries and significantly associated with death. Nevertheless, no consistently effective and commercially available chemotherapeutic agents or vaccines exist to treat or prevent infection. Recently, phenotypic screening efforts with a focused library identified pyrazolopyridines, calcium dependent protein kinase inhibitors, and other new classes of low molecular weight compounds that inhibit Cryptosporidium and are active against both Cryptosporidium parvum and C. hominis. These compounds have demonstrated in vivo efficacy in mouse and neonatal calf models. Neonatal calves experimentally infected with C. parvum and treated with these inhibitors had significant decrease in parasite shedding and rapid resolution of diarrhea and dehydration. The planned research will help to refine molecule development in order to reduce systemic circulation of the drug, which will improve drug safety for use in calf and pediatric populations. A total of 59 calves will be enrolled at birth, randomized to treatment or control group, challenged with parasite, and followed for up to 23 days post-infection. The study will gather data on the pharmacokinetics and pharmacodynamics of the molecule, as well as measure efficacy. Primary study end-points include: reduced severity of diarrhea, fecal oocyst shedding, and dehydration. We anticipate that calves treated with these novel compounds will have significant improvements in primary and secondary end-points in comparison to controls.