SUMMARY: The thyroidal uptake of 36ClO4− and the effect of stable perchlorate ion and functional state of the thyroid, such as after long-term administration of propylthiouracil (PTU) or after hypophysectomy, on the uptake of 36ClO4− were studied in rats and guinea-pigs. Based on the analysis of uptake curves, radioactive inulin and sulphate spaces, and histological measurements of compartmental sizes of the thyroid, the relative concentrations of 36ClO4− in the various compartments were calculated and compared with those of 36Cl-. The passage of 36ClO4− and 36Cl− across both the basal and the apical membranes of the follicular cells in the different conditions were analysed. The results suggest that 36ClO4− is concentrated in the lumen of the thyroid by a two-step process. It is actively transported across the basal cell membrane from the interstitial fluid into follicular cells, and is further concentrated in passage across the apical membrane into the lumen. The evidence suggests that the latter process is also an active one.