Using a quantitative immunocytochemical technique, antral gastrin cell populations in the rat were studied in various states of thyroid function. Simultaneous determinations of circulating serum gastrin were made by RIA. Rats made hypothyroid by ingestion of methimazole (0.01% solution in drinking water for 30 days) demonstrated a significant 32% decrease in gastrin cell density (306 +/- 9/cm vs. 207 +/- 11/cm for controls) associated with a significant 50% decrease in serum gastrin (143 +/- 12 vs. 307 +/- 20 pg/ml for controls). Induction of hypothyroidism and hypoparathyroidism by surgical thyroparathyroidectomy resulted in similarly significant decreases in gastrin cell numbers (229 +/- 12/cm) and serum gastrin (169 +/- 14 pg/ml). Animals that underwent thyroparathyroidectomy followed by T4 replacement (2.5 micrograms/100 g X day, ip) for 30 days had a mean gastrin cell density that was not significantly different from that of controls; serum gastrin was decreased to 207 +/- 11 pg/ml. The administration of excess T4 (200 micrograms/100 g X day, ip) for either 15 or 30 days was associated with a significant increase in gastrin cell numbers (413 +/- 23/cm at 15 days; 352 +/- 21/cm at 30 days). Mean serum gastrin was increased by 82% after 15 days of T4 administration (558 +/- 51 pg/ml) and by 65% at 30 days (506 +/- 36 pg/ml). We conclude that T4 is trophic for gastrin cells in the rat.