The effects of ventral tegmental area of Tsai (VTA) stimulation on lateral hypothalamic (LH), lateral preoptic area (LPA). and medial hypothalamic neuronal activity were determined in anesthetized rats. Recordings from 81 hypothalamic neurons indicate that stimulation produces predominantly decreases in hypothalamic neuron activity. Increase in activity due to VTA stimulation occurred less frequently. Following single rectangular pulse stimulation, 0.5 msec. 0-500 microA, short latency decreases in activity occurred. Longer latency increases in discharge frequency were also observed. Dose response relations were established for 56% of the LH neurons, 78% of the LPA neurons, and for 82% of the medial hypothalamic neurons following VTA stimulation. Decreases and in a few cases increases in activity seemed to involve only one or two synapses. Antidromic responses verified interconnections between the VTA and the hypothalamus and revealed relatively slow conduction velocities of 0.45 and 0.81 m/sec. The changes in discharge frequency which occurred following VTA stimulation were similar in direction to the effects of the direct microiontophoretic application of dopamine (DA) or norepinephrine (NE). Since DA increased or decreased while NE decreased discharge frequency, these microiontophoretic tests indicated that the shorter latency VTA stimulation induced increases in decreases in neural activity were associated with VTA dopaminergic neuron stimulation and that in some cases short and long latency decreases in neuronal activity were due to activation of VTA ventral bundle NE fibers of passage or to indirect polysynaptic mechanisms. Results demonstrate the interconnections between various regions of the hypothalamus and the VTA along the extent of the medial forebrain bundle (MFB). The cross-validation of neuroanatomical and various electrophysiological methods in establishing the nature of hypothalamic connections was discussed.