Activity of neurones of the rat medial septal nucleus (m.s.) was recorded in in vitro slice preparations. The recorded population could be divided into low (less than 30 M omega)- and high-input-resistance (greater than 30 M omega) neurones. The high-resistance neurones tended to fire spontaneous action potentials and post-synaptic potentials. Some of the spontaneously active cells fired rhythmically at rates of 2-10 Hz. The rhythmicity disappeared following hyperpolarization of the recorded cell. The cells could fire repetitive Ca2+ spikes in the presence of tetrodotoxin (TTX) and intracellular Cs+. Cd2+ blocked this rhythmicity. Most of the m.s. cells had a non-linear voltage-current relation in both the hyperpolarizing and depolarizing directions. Hyperpolarizing rectification was selectively blocked by extracellular Cs+ whereas depolarizing rectification could be blocked by TTX. A recovery from hyperpolarization was associated in many cells with a transient depolarization (anodal break (a.b.) potential). A 20 ms 15 mV hyperpolarization could trigger an a.b. potential. The a.b. potential was reduced by TTX and Cs+ but not by Cd2+ or Mn2+. Depolarization of quiescent neurones triggered action potential discharges. A common pattern of discharge was a burst of two spikes which kept a fairly constant interspike interval. The second spike in a doublet could not follow a rate of 10 Hz depolarizing current pulses. It was also sensitive to topical application of Cd2+. It is therefore suggested that Ca2+ might be involved in the generation of the doublet. Long depolarizing current pulses produced trains of action potentials, showing little accommodation and little after-hyperpolarization, indicating that these cells possess little Ca2+-dependent K+ current. Many cells emitted spontaneous post-synaptic potentials at high rates. These could be blocked by picrotoxin. Stimulation of the lateral septal (l.s.) nucleus produced a Cl-dependent i.p.s.p. The i.p.s.p. was blocked by picrotoxin. Topical application of gamma-aminobutyric acid (GABA) produced a marked Cl(-)-dependent increase in conductance. It is suggested that l.s. projects a GABA-mediated inhibitory connexion to the m.s. Acetylcholine (ACh) depolarized m.s. neurones and caused an increase in input resistance. The response was present in TTX or Cd2+-containing medium. Atropine blocked responses to ACh. 5-Hydroxytryptamine (5-HT) hyperpolarized m.s. neurones in a manner consistent with an increase in K+ conductance. The effects of 5-HT were seen in TTX- and Cd2+-treated m.s. slices.(ABSTRACT TRUNCATED AT 400 WORDS)