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The African sharptooth catfish Clarias gariepinus lives in freshwater, is an obligatory air breather, and can survive on land during drought. The objective of this study was to elucidate how C. gariepinus defends against ammonia toxicity when exposed to terrestrial conditions. During 4 d of aerial exposure, there was no accumulation of urea in its tissues, and the rate of urea excretion remained low. Thus, exposure to terrestrial conditions for 4 d did not induce ureogenesis or ureotely in C. gariepinus. Volatilization of NH(3) was not involved in excreting ammonia during aerial exposure. In addition, there were no changes in levels of alanine in the muscle, liver, and plasma of C. gariepinus; nor were there any changes in the glutamine levels in these tissues. However, there were extraordinarily high levels of ammonia in the muscle (14 micromol g(-1)), liver (18 micromol g(-1)), and brain (11 micromol g(-1)) of fish exposed to terrestrial conditions for 4 d. This is the first report on a fish adopting high tolerance of ammonia in cells and tissues as the single major strategy to defend against ammonia toxicity during aerial exposure. At present, it is uncertain how C. gariepinus tolerates such high levels of ammonia, especially in its brain, but it can be concluded that, contrary to previous reports on two air-breathing catfishes (Clarias batrachus and Heteropneustes fossilis) from India, C. gariepinus does not detoxify ammonia to urea or free amino acids on land.