Neurotensin (NT) is a 13 amino-acid peptide which is both a hormone and neuromodulator. Through its 3-4 known receptors, NT is shown to influence several physiological responses including autonomic output, hydromineral balance, and cardiovascular regulation. Recent transcriptomic studies have revealed that the subfornical organ (SFO) expresses a high abundance of neurotensin receptors (NTSR), specifically NTSR2 and NTSR3, with levels comparable to other prominent neuromodulators that act in this region. The SFO is known for its involvement in cardiovascular regulation, sympathetic output, and hydromineral balance. As a circumventricular organ, it lacks the blood brain barrier, providing a direct interface with peptides in circulation, in addition to centrally released signals in cerebrospinal fluid. Both NT and the SFO have been found to influence satiety and water intake; thus, the SFO, through various peptides, and NT as a peptide have both been found to play a key role in hydromineral balance; which, in turn, plays a role in cardiovascular regulation. Due to their intersecting areas of influence, and as the SFO is a major integration center for peripheral and central signals, we hypothesized that this neuropeptide modulates neurons in this region to elicit physiological responses. Whole-cell patch-clamp recordings from this study demonstrate that NT (1µM) modulates synaptic activity in 54% (34/63) of SFO neurons tested, in acutely prepared brain slices. Specifically, we found that NT significantly increased excitability of SFO neurons by depolarizing the resting membrane potential, and that NT decreased the amplitude of EPSCs, but not EPSC interevent interval. By also treating 35/63 cells previously tested for NT, with Ang II, we found that there appears to be a subpopulation of SFO neurons sensitive to both NT and Ang II. Most of these cells exhibited a decrease in EPSC amplitude to both peptides, suggesting that they may operate through this region of the CNS to affect the same homeostatic mechanisms.