The possibility that pseudopods might provide a mechanism by which newly synthesized, hormone-poor thyroglobulin recently delivered to the follicle lumen escapes immediate reuptake and degradation was explored. The study was performed with EM autoradiography on rats pretreated with T4 [thyroxine] for 2 days and injected with [3H]leucine or Na125I. Pseudopods were induced by the injection of TSH (100 mU) 20 min before perfusion fixation. The density of autoradiographic grains in colloid droplets located in pseudopods was compared with the grain density in different regions of the follicle lumen. In rats injected with radioleucine 1.5 and 3 h before TSH injection, the grains were distributed in a gradient in the lumen periphery. Seventy to 80% of the grains were located over the microvillus region. The grain density over colloid droplets in pseudopods was abut 10% of that over the microvillus region an similar to the density at a distance 1-2 .mu.m from the microvillus region. After injection of Na125I, 40 min before TSH, the grains were more widely spread in the lumen, but still formed a gradient in the lumen; about 30% of the grains were associated with the microvillus region. Again, the grain density over colloid droplets in pseudopods was about the same as that at a distance 1-2 .mu.m from the microvillus region. The observations are compatible with the idea that pseudopods collect thyroglobulin located at some distance from the apical surface. This, together with the circumstance that newly synthesized thyroglobulin is located close to the apical plasma membrane, might provide a mechanism of selective macropinocytosis by which newly synthesized thyroglobulin recently delivered to the follicle lumen is prevented from immediate reuptake.