This work was aimed at elucidating the effect of thyroid function on the physiology and biochemistry of the islet-cell population within the endocrine pancreas. To this end, we performed a comparative study of the physiochemical properties of islet-cell membranes and of the dynamics of glucose-induced insulin secretion in isolated pancreatic islets prepared from euthyroid i.e. control (C), hypothyroid (H), and thyroxin-supplemented hypothyroid (HT) rats. H rats were obtained by injecting normal rats with 131iodine, while HT rats consisted of H rats treated with thyroxin (T4). Insulin secretion was studied in isolated islets perifused with 3.3 and 16.6 mM glucose. Physicochemical properties of the partially purified islet plasma membranes were assessed by measurements of fluorescence polarization with the fluorophore 1,6-diphenyl-1,3,5-hexatriene (DPH) as a lipidic molecular probe. Insulin output during either the first or second phase of insulin secretion in H islets was significantly lower than in C islets. The slope of the curve in the second phase of insulin secretion was also lesser in H than in C islets, suggesting an additional defect in their velocity of hormone release. T4 administration of H rats reversed the decrease in insulin output to the range found in C islets but was incapable of correcting the defect in the hormone-secretion velocity. Several changes were found in the physicochemical properties of the membranes obtained from H islets as compared to C islets.(ABSTRACT TRUNCATED AT 250 WORDS)