The effects of 24 h of exposure to underwater anoxia and 15 days of estivation (at 26–27°C) on the enzymatic antioxidant system of the hepatopancreas of the freshwater snail Biomphalaria tenagophila (Planorbidae) are described. The effect of 24 h of recovery was also investigated. Catalase activity dropped by 31% during 24 h of anoxia, and superoxide dismutase (SOD) activity was reduced by 43% during the 15 days of estivation. This is consistent with the overall decrease in metabolic rate during estivation or anoxia. Indeed, the heartbeat diminished by 28–36% during estivation (determination was possible for only 4 days) and by 66% after 24 h of anoxia. On the other hand, selenium-dependent glutathione peroxidase (Se-GPX) activity increased during anoxia (from 10 to 14 mU/mg protein) and estivation (by 14%). Glutathione S-transferase (GST) and glutathione reductase activities remained unchanged during estivation and anoxia. Glucose 6-phosphate dehydrogenase activity was unchanged during estivation and recovery. Recovery restored SOD activity. Catalase, Se-GPX, and GST activities during recovery were significantly lower than those of the respective controls. Lipid peroxidation, determined as the level of thiobarbituric acid-reactive substances, was unchanged in the hepatopancreas after 15 days of estivation and 26 h of recovery from estivation. It is possible that the increase in Se-GPX activity during anoxia and estivation, and the maintenance of GST activity, are relevant in minimizing the effects of reactive oxygen species that can be formed upon resumption of aerobic metabolism. Thus, B. tenagophila may have a biochemical strategy of preparation for oxidative stress such as that observed in several other species of anoxia/hypoxia-tolerant animals.