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The elevation in plasma angiotensin-converting enzyme (ACE) levels observed in patients with hyperthyroidism is unexplained. In this study three hypotheses were investigated. Results from a study using rats treated with thyroid hormones indicated that the increased ACE was not due to increased cleavages of enzyme from lung endothelia. Data from patients with specific tissue damage argue against a nonspecific release of ACE from damaged cells. Data from cultured cell experiments, however, strongly support a direct effect of thyroid hormones upon ACE synthesis and secretion.