Neurotensin administered intravenously in a dose of 1 nmole/kg produced triphasic blood pressure responses in anesthetized rats: the first depressor, second pressor and third depressor responses. The first depressor response was significantly suppressed by treatment of animals with a mixture of diphenhydramine and metiamide or chronic administration of compound 48/80, but was not modified by treatment with atropine, phentolamine, yohimbine, propranolol, sulpiride and adrenalectomy. The second pressor response was abolished by phentolamine, yohimbine and adrenalectomy. The second phase response was also markedly reduced by diphenhydramine in reserpinized rats and chronic administration of compound 48/80. The third depressor response was blocked by treatment of animals with diphenhydramine or chronic administration of compound 48/80. These results suggest that neurotensin may produce an immediate depressor response (the first phase) partly through a histamine-mediated process, and the second pressor response is produced by catecholamines released from the adrenal medulla through a histamine-mediated process. The third depressor response appears to be mediated mainly by histamine. The participation of mast cells as an origin of histamine which mediates these processes is suggested.