Digestion of large meals in pythons produces substantial increases in heart rate and cardiac output as well as a dilation of the mesenteric vascular bed leading to intestinal hyperemia but the mediators of these effects are unknown. Bolus intraarterial injections of python neurotensin ([His³, Val⁴, Ala⁷]NT) (1 - 1000 pmol kg^-1) into the anesthetized ball python Python regius (N = 7) produced a dose-dependent vasodilation that was associated with a decrease in systemic pressure (P_sys) and increase in systemic blood flow (Q_sys). There was no effect on pulmonary pressure and conductance. A significant (P < 0.05) increase in heart rate (f_H) and total cardiac output (Q_tot) was seen only at high doses (> 30 pmol kg^-1). The systemic vasodilation and increase in Q_tot persisted after -adrenergic blockade with propranolol but the rise in f_H was abolished. Also, the systemic vasodilation persisted after histamine H₂-receptor blockade. In unanesthetized pythons (N = 4), bolus injection of python NT in a dose as low as 1 pmol kg^-1 produced a significant increase in blood flow to the mesenteric artery (177 % ± 54 %; mean ± S.E.M.) and mesenteric conductance (219 % ± 74 %) without any increase in Q_sys, systemic conductance, P_sys, and f_H. The data provide evidence that NT is an important hormonal mediator of postprandial intestinal hyperemia in the python but its involvement in mediating the cardiac responses to digestion may be relatively minor.