Toxoplasmosis and cryptosporidiosis are the most common causes of hospitalization and opportunistic infection in patients with AIDS. Toxoplasma and Cryptosporidia, parasites with worldwide distribution, are also pathogens of significant economic importance in livestock where they cause abortion, diarrhea, weight loss and death. Artemisinin (qinghaosu) and certain derivatives have shown significant antiparasitic activity for the related disease malaria and for toxoplasmosis and cryptosporidiosis in Phase I SBIR and independent studies. Synthesis and evaluation of additional derivatives followed by correlation of results to pharmacological factors leading to high therapeutic index are necessary steps toward commercialization of an effective agent. The proposed research will focus on C-12 and endoperoxide functional derivatives of artemisinin that will be synthesized and evaluated for inhibition of growth of Toxoplasma gondii and Cryptosporidium parvum by proven in vitro and in vivo methods. The proposers have a supply of artemisinin on hand, have successfully synthesized derivatives, have the necessary technical background to interpret results, have proven natural product and derivative GMP manufacturing capabilities, and are committed to participate in commercialization. The proposed Phase II program meets the technical objectives of a recent NIAID call for the discovery of drugs for the treatment of opportunistic infections associated with AIDS.