Prolonged fasting and longer time between dosing and sampling reduced the plasma gastrin concentrations after omeprazole (80 mumol/kg x 2 for 14 days) treatment in male rats whereas the amounts of tissue gastrin were essentially unchanged during these initial experiments. After 28 days omeprazole (80 mumol/kg x 2) or ranitidine (375 mumol/kg x 4) that produced corresponding inhibition of acid secretion, increased the tissue gastrin content by 114 and 59%. A low dose of omeprazole (20 mumol/kg x 2) also raised the gastric gastrin content (41%), whereas no change was noted on treatment with a low dose of ranitidine (125 mumol x 4). Following recovery for 28 days no significant increases in gastrin were observed. 1, 3, 7, 14 or 28 days of treatment with omeprazole (80 mumol/kg x 2) gradually increased the gastric gastrin content being significantly raised already after 3 days. We conclude that a) measuring the tissue gastrin content may be the preferable method when changes in gastrin following long-term treatment with acid inhibiting drugs are to be determined, b) the amount of gastrin in the stomach increases rapidly following treatment with omeprazole and is approximately doubled following 28 days of treatment and c) after treatment for 28 days omeprazole was found to cause greater elevations in the tissue gastrin content than ranitidine despite similar degrees of basal acid inhibition.