This work investigates the effects of hypophysectomy and replacement treatment with mammalian pituitary preparations (ACTH, TSH, prolactin, growth hormone, alpha-MSH) and cortisol and thyroxine, on the structure and function of the interrenal in the teleost Poecilia latipinna. In long-term (3–4 weeks) experiments, histological studies showed that hypophysectomy induced involution of the interrenal, which was prevented by treatment with ACTH. TSH also opposed this interrenal involution, but it was not as strongly mitogenic as ACTH. MSH, prolactin, growth hormone, and thyroxine had no effect on the involuted interrenal of hypophysectomized fish. Hypophysectomy also resulted in hypertrophy of the liver, elevated hepatic glycogen concentrations, and a reduced number of circulating leucocytes. All these changes were prevented by ACTH and cortisol, both of which also exacerbated the weight loss that followed pituitary ablation. MSH was not tested on leucocyte count, but it had no effect on liver weight, liver glycogen, and body weight loss. Both TSH and thyroxine increased the leucocyte count, and in addition thyroxine reduced liver weight and exacerbated body weight loss. Prolactin at high dose reduced liver weight, but did not affect liver glycogen and the leucocyte count, while at the highest dose it ameliorated body weight loss. Growth hormone at high dose reduced liver weight, but had no action on liver glycogen, leucocyte count, and body weight loss. Thus, only TSH seems able to mimic the effects of ACTH on interrenal structure. Its stimulatory effect on circulating leucocytes could be thyroid-mediated, since thyroxine has the same effect in the absence of any action on interrenal morphology. The actions of growth hormone and prolactin on liver weight would appear to be direct. In short-term (30 min) tests on hypophysectomized fish, ACTH, prolactin, TSH, growth hormone (porcine and human), and alpha-MSH all elevated plasma cortisol levels, reduced to near-zero by hypophysectomy 48 hr previously. Bovine serum albumin did not elevate plasma cortisol levels. The data are discussed bearing in mind the possibility of other pituitary hormones mimicking the actions of teleostean ACTH, on the one hand, and, on the other hand, the possibility of minute contamination of the hormone preparations with ACTH. This second possibility cannot be discounted in considering the cortisol-elevating properties of all the hormone preparations used in the short-term tests, but there are no compelling reasons for accepting it as explanation of the ability of TSH preparations to maintain interrenal morphology. The findings emphasize the difficulties inherent in using mammalian hormone preparations to deputise for fish pituitary hormones.