The effect of 2-deoxy-D-glucose (2-DG), a carbohydrate analogue, on growth, respiration and fine structure of Herpetomonas samuelpessoai is described. In a glucose-free medium, 2-DG inhibited growth down to 7% that of the control. In presence of equal concentrations of glucose, the inhibition by 2-DG was 55%. With 5 times as much 2-DG as glucose, the inhibition was 88%. Increase in 2-DG in relation to glucose resulted in a progressive inhibition of H. samuelpessoai. Only glucose, fructose of glycerol reversed the inhibition caused by 2-DG in H. samuelpessoai. Glucose was more active than glycerol and fructose. Protection against 2-DG toxicity was confirmed by respirometry experiments. Oxidation of glucose was less affected by 2-DG than that of fructose and glycerol. In presence of 2-DG the cells became round to oval and showed some granules in the cytoplasm. In control cells the mitochondrial cristae were short and straight while in cells treated with 2-DG they were longer and curved. Morphometric analysis of electron micrographs showed that the mitochondrial relative volume of normal cells was 0.084 +/- 0.018 while in treated cells were 0.166 +/- 0.030. Results are discussed in relation to the carbohydrate metabolism and the mode of action of 2-DG.