Analytical ion microscopy was used to evaluate the quantitative changes in thyroid127I mapping induced by amiodarone in relation to the iodine intake. Mice were maintained on a normal diet (NID), on a low iodine diet (LID) or on a high iodine diet (HID) during 3 months. They received daily ip injections of amiodarone or Nal during the last 10 days. Microanalysis of iodine was performed on thyroid sections. In NID mice, the cellular127I concentration (mean ± SE: 0.90 ± 0.06 µg/mg) was lower than that of follicular lumina (6.99 ± 0.17). Amiodarone increased cellular concentration (2-fold) and decreased follicular concentration; Nal induced the same results. In LID mice, both concentrations, which were decreased 60- to 70-fold in comparison with NID, were restored by amiodarone, while Nal enhanced follicular concentration more than amiodarone. In HID mice, the follicular concentration (1.5-fold higher than normal) returned to a normal range with amiodarone, but cellular concentration (2.5-fold lower than normal) remained low, while Nal increased the cellular concentration 3- fold.These data show that iodine released by amiodarone has a bioavailability different from that of Nal. They indicate that thyroid response to amiodarone is related to dietary iodine intake, which, in turn, determines autoregulatory mechanisms. They also raise the question of the possible existence of an intrinsic property of amiodarone which would explain the specificity of its activity on thyroid iodine organification and the development of amiodarone-induced human thyroid diseases. © 1990 by The Endocrine Society.