OBJECTIVE Thyroid hormones affect gastric acid secretion. As the mechanism of this effect has not been fully known, in this experimental study the isolated gastric acid secretion of hypothyroid and hyperthyroid rats were compared with control group by the administration of different doses of pentagastrin, histamine and carbachol as gastric acid secretion stimulators. METHODS This study was carried out in Ahwaz University of Medical Sciences, Ahwaz, Iran in the year 2000. Each group were consisted of 8 rats (N-mari) of both sexes with a mean weight of 246 +/- 5 grams. Hypothyroid and hyperthyroid states were induced respectively by adding methimazole (500 mg/liter) for 20 days and thyroxin (500 microg/liter) for 35 days in animals drinking water. After general anesthesia, by intraperitoneal injection of sodium thiopental (50 mg/kg body weight), celiotomy was carried out quickly. The end of esophagus was tied and a silicon tube (2-2.5 mm) was entered into the stomach via duodenum and fasted in pylor region. The stomach was isolated by cutting the esophagus proximal to the tied region and the proximal part of duodenum and put into cold serous solution. After washing the serous and mucus surfaces by serous and mucus solutions, the stomach was transferred immediately to a tissue bath containing warm serous solution (V= 40 ml, T= 37 degrees C). Gastric acid secretion in isolated stomach stimulated by pentagastrin, carbachol and histamine was measured by wash out technique and automatic titrator. Moreover, to study the effect of thyroid hormones on gastric acid secretion a number of dose-dependent experiments after the administration of different doses of histamine (50, 100, 150, 200 micromol), carbachol (50, 100, 150, 200 micromol), and pentagastrin (30, 60, 90, 120 ug/kg body weight) were performed. RESULTS Both basal and histamine, carbachol, pentagastrin stimulated-acid secretion decreased and increased in hypothyroid and hyperthyroid groups compared with control group. CONCLUSIONS It seems that thyroid hormones have not exert their effects by changing the cholinergic, gastrin and histamine receptors but probably by alerting the number or size of the secretory cells in stomach.