Freshwater catfish, Heteropneustes fossilis, were subjected to 42 mg L À1 of azadirachtin for short-term exposure (96 h) and to 10.5 mg L À1 for long-term exposure (28 days). Six fishes were sacrificed on each time interval from control and experimental groups after 24, 48, 72, and 96 h in the short-term exposure and after 7, 14, 21, and 28 days in the long-term experiment. The calcium regulating endocrine gland, viz. the ultimobranchial gland, was fixed for histological studies. Up to 72 h of azadirachtin treatment, there was no histological alteration in the UBG (ultimobranchial gland) of H. fossilis. After 96 h exposure, the ultimobranchial cells stain feebly and the nuclear volume of these cells were slightly decreased. No histological alterations have been observed in the UBG cells up to 14 days following azadirachtin exposure. After 21 days, the cytoplasm of ultimobranchial cells was feebly stained and the nuclear volume exhibits a decrease. The nuclear volume of these cells was further decreased and the gland shows vacuolization and degeneration at certain places after 28 days azadirachtin treatment. Hence, it can be concluded that azadirachtin severely affects the physiology of calcium homeostasis in H. fossilis. Therefore, the botanical pesticides should be used carefully near aquatic reservoirs.