Hydrogenosomes of the anaerobic flagellate Tritrichomonas foetus can use oxygen as terminal electron acceptor in pyruvate metabolism. In particles broken with the detergent, Triton X-100 or by repeated freezing and thawing, pyruvate-supported respiration is greatly enhanced by coenzyme A. Additions of small amounts of CoA result in a phenomenon resembling respiratory control. ADP and GDP also have a stimulatory effect; however, the rate of respiration in the presence of saturating concentrations of CoA is always much higher than with saturating concentrations of ADP or GDP. The results suggest that the availability of CoA as acetyl acceptor is the primary controlling factor of pyruvate oxidation and that the observed effect of nucleotide diphosphates (Cerkasov, J., Cerkasovová, A., Kulda, J., and Vilhelmová, D. (1978) J. Biol. Chem. 253, 1207-1214) is explained by their participation in reactions that liberate CoA from acyl-CoA complexes in connection with substrate level phosphorylation.