One of the earliest responses of the thyroid cells to TSH is macropinocytosis with formation of intracellular colloid droplets. We demonstrate here that increasing stimulation with TSH not only elicits a highly individual macropinocytotic response among different follicular cells but that the fraction of TSH-responsive cells is also a function of the TSH dose. After pretreatment with T4, mice and rats were injected ip with bovine TSH and killed 2 h later. The macropinocytotic response to TSH was evaluated on periodic acid-Schiff-stained 3-microns sections of the thyroids in terms of droplet number per 25 follicles and, in addition, by assessing recruitment, i.e. percentage of droplet-containing cells. Both variables increased with increasing TSH stimulation until they reached a plateau at about 9 mU TSH in mice and at about 300 mU TSH in rats: the percentage of droplet-containing cells gradually increased in mice from 2% (no TSH) to 67% (9 mU TSH) and in rats from 11% (no TSH) to 54% (300 mU TSH). Overall pinocytotic response as well as thyrocyte recruitment could be modified by extra- and intrathyroidal factors: for example, pretreatment of the mice with an iodine-deficient diet increased the maximal percentage of droplet containing cells to nearly 90%. Obviously, two separate components of the macropinocytotic response of the thyroid gland to TSH can be distinguished: the first is the gradually increasing fraction of droplet-containing cells, the second is the well known increase of the number of colloid droplets in each TSH-responsive cell with progressive TSH stimulation. Recruitment of thyrocytes with a gradually increasing natural threshold to a hormonal stimulus appears to be a fundamental mechanism in the thyroid gland and possibly in other organs.