The in vivo activation of rat thyroid follicle cells by increasing doses of TSH (1-100 mU) was studied by quantitative light and electron microscopy. The number of pseudopods induced after 20 min by 5, 20, 50 and 100 mU was the same but a dose-dependent increment of the individual pseudopod size (measured as profile area or membrane surface area) was observed, suggesting a graded response in the individual follicle cell. The number of pseudopods induced by 1 mU was only 10% of that in the other group. Another early effect of TSH, besides the induction of psuedopods, is stimulation of exocytosis. The number of exocytotic vesicles in pseudopod-bearing follicle cell profiles (the presence of a pseudopod taken as a sign of activation) decreased in a dose-dependent manner. This indicates that the follicle cell does not respond in an all-or-none mode (in which case a similar decrease in vesicle number in activated cells should be expected irrespective of the level of TSH) and that the response in the individual cell is graded depending on the level of TSH stimulation.