The goal of these studies is to increase understanding of the pathogenesis of parasitic diseases and to improve their diagnosis, therapy and prevention. In addition to studies at NIH, clinical investigation of patients has been carried out in the endemic areas of Guatemala (onchocerciasis), India and Brazil (filariasis), Benin (loiasis), Zaire and Jamaica (strongyloidiasis), Honduras (leishmaniasis) and Panama (leishmaniasis). Laboratory studies have permitted definition of the regulatory and pathogenetic mechanisms underlying the IgE, IgG4, and eosinophil responses to helminth infection, as well as the identification of molecules responsible for antigenic variation in giardiasis and likely involved in protective immunity in bancroftian filariasis, onchocerciasis and strongyloidiasis. A diagnostic test to detect new and prepatent onchocerciasis infections has been developed using a purified recombinant 16 kD protein (OV-16). Controlled clinical trials of ivermectin for bancroftian filariasis have shown it to be almost as effective as the older antifilarial drug diethylcarbamazine, and equally safe in clearing microfilaremia; because of its single-oral-dose mode of therapy, it should be considerably more practical for use in control programs than diethylcarbamazine has been.