Peroxidase activity in various human benign and malignant pathological conditions has been investigated. The activity was measured in vitro by oxidation of iodide and by iodination of bovine serum albumin (BSA). The deficiency of hormone synthesis observed in various diffuse benign thyroid disorders was certainly not due to a lack of peroxidase activity. In hyperthyroid patients treated with carbimazole and in a euthyroid state at surgery, iodide-peroxidase activity (24 patients) and DNA content (12 patients), both expressed per g of wet weight, were enhanced (288% and 122% increases over control, respectively) and the cellular enzyme activity was almost double than that of normal tissue. An increase in peroxidase activity when measured by iodination of BSA (11 patients) was also observed (350% increase over control). It is suggested that high cellular peroxidase activity might be due not to the treatment but to the disease. In euthyroid patients with diffuse sporadic goiter, the peroxidase activity measured by oxidation of iodide (29 patients) and by iodination of BSA (13 patients) was almost twice that of normal tissue while the DNA content (17 patients) was the same. In these two diffuse pathological benign conditions and in normal gland an inverse relationship has been found between cellular enzymatic activity and iodine content. In the group of sporadic goiter itself, this correlation was also observed. In contrast, no correlation was found between peroxidase activity and iodine content in localized benign lesions. In “hot” nodules (15 cases) a statistical increase in iodide peroxidase activity was observed and the DNA content was also enhanced (7 patients). However, in “cold” nodules the DNA content was not statistically different from normal (12 patients), and the cellular iodide-peroxidase activity was higher in this disease than in any other benign thyroid disorders. On the other hand, when measured by iodination of BSA, no statistical increase in peroxidase activity was found. In the 16 cases of differentiated carcinomas studied, the results were variable but in most cases, the peroxidase activity, measured by oxidation of iodide as well as by iodination of BSA, was below that of normal tissue. In more than 50% of the cases, no detectable activity was found and no relationship was observed between the iodine content of the malignant tissue and the peroxidase activity. In contrast with the benign pathological conditions, the peroxidase was lower than normal only in cancerous tissues.