We studied the effect of pentagastrin on histamine content of gastric mucosa obtained from dogs with gastric fistulas to determine whether pentagastrin mobilizes cellular stores of histamine. Experiments were also performed on canine gastric mucosa in vitro to investigate the effects of pentagastrin on histamine release, per se. During in vivo studies basal histamine content averaged 0.9 nmol/mg wet wt tissue or 18.8 nmol/mg tissue prot. No significant difference in gastric mucosal histamine content occurred during intravenous administration of pentagastrin (6 or 16 micrograms . kg-1 . h-1) or saline (control), even though acid output from the gastric fistula increased significantly above control during pentagastrin infusion. Moreover, pentagastrin (10(-5) and 10(-8)M) did not release more histamine from gastric mucosa in vitro than the buffer (control), whereas Triton X-100 and the phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, alone and in combination with calcium ionophore A23187, released significant amounts of histamine above control values. From these experiments we conclude that pentagastrin did not alter histamine content of canine gastric mucosa in vivo, even though acid secretion was stimulated maximally, nor did pentagastrin release histamine in vitro.