Parasitic helminths pose significant health problems throughout the world but, in many cases, adequate means of chemotherapy still are not available. It is clear that many helminths exhibit a predominantly anaerobic energy metabolism which differs substantially from that of the host, and it appears that many potent anthelmintics specifically interfere with helminth energy metabolism. However, before the differences between host and parasite can be fully exploited, the energy-generating reactions operating in these parasites need to be examined in more detail. The present study is designed to characterize the regulation and energetics of volatile fatty acid synthesis in mitochondria isolated from the porcine nematode, Ascaris suum. This organism has served as an excellent model for many studies of helminth metabolism. Its mitochondria function anaerobically, using unsaturated organic acids, instead of O2, as terminal electron-acceptors and it excretes acetate, propionate and the branched-chain fatty acids (BFA), 2-methylbutyrate and 2-methylvalerate, as end products of carbohydrate degradation. However, little is known about the factors controlling their formation. In the present study, the rates of pyruvate decarboxylation and BFA formation in intact mitochondria will be correlated with the activity state of the pyruvate dehydrogenase complex and the levels of a number of physiologically important intramitochondrial metabolites. In addition, pyruvate dehydrogenase phosphatase and the membrane-bound electron-transport components involved in BFA synthesis will be isolated and characterized. Since all helminths exhibiting anaerobic mitochondrial metabolisms excrete acetate and contain similar electron-transport systems, these studies should have broad application. Hopefully, once the enzymatic differences between host and parasite metabolism have been identified and evaluated, a more sensible approach to chemotherapy can be adopted. In addition, the more that is known about the biochemical mode of action of anthelmintics, the more rational efficient drug usage will become.