Participation of both the lateral septum and the medial hypothalamus in similar behavioral and homeostatic functions, combined with anatomical data indicating a modest descending lateral septum projection to medial hypothalamic areas, prompted an investigation of the electrophysiology of lateral septum--medial hypothalamic connections in pentobarbital-anesthetized male Sprague-Dawley rats. Field potentials evoked by lateral septum stimulation were prominent within the hypothalamic ventromedial nucleus: their distribution closely overlapped with amygdala-evoked field potentials. Lateral septum stimulation evoked orthodromic responses from 67% of 800 medial hypothalamic and preoptic neurons (55.5% excitatory, latency 17.5 +/- 0.5 ms; 11.5% inhibitory, latency 19.1 +/- 1.4 ms), including 15 of 31 tuberoinfundibular neurons activated antidromically from the median eminence, 37.4% of cells responded orthodromically to both lateral septum and amygdala stimulation, whereas only 5.8% of cells demonstrated orthodromic responses to both lateral septum and midbrain periaqueductal gray stimulation. These observations suggest that lateral septum neurons influence the excitability of many medial preoptic and hypothalamic neurons, and indicate a convergence of lateral septum and amygdala influences onto 37% of medial hypothalamic cells. In the rat, the lateral septum's influence on adenohypophyseal hormone secretion appears to be mediated indirectly, i.e. through monosynaptic connections with medial hypothalamic tuberoinfundibular neurons.