We have previously reported that flushing associated with a gastric carcinoid tumor can be provoked by pentagastrin and inhibited by either somatostatin or combined histamine H1- and H2-receptor blockade. In this report, the effects of pentagastrin and somatostatin on histamine release in a patient with a metastatic gastric carcinoid tumor were examined. Small doses of intravenous pentagastrin (0.1-0.4 micrograms) produced a dose-dependent increase in the level of circulating plasma histamine. Graded infusions of somatostatin suppressed both basal and pentagastrin-stimulated plasma histamine levels in a dose-dependent fashion. A close correlation was found between circulating plasma histamine levels and attendant changes in blood pressure and pulse rate. This study documents that pentagastrin directly evokes the release of histamine from this patient's gastric carcinoid tumor and that the release of histamine is inhibited by somatostatin. In addition, this study provides additional evidence that the primary mediator of the flushing in this patient with foregut carcinoid syndrome is histamine.