The distribution both of Met-enkephalinergic nerve terminals and of calbindin-containing neurons was investigated in the guinea-pig lateral septum, using a double-immunostaining technique. The findings show that the two immunoreactivities overlapped for neurons located in areas of the dorsal part and of the mediolateral part of the lateral septum. Nine cells of the mediolateral part which were electrophysiologically characterized and intracellularly labelled were subjected to the double-immunostaining protocol. All these cells displayed characteristic discharges due to the activation of high-threshold Ca2+ conductances. Two of them contained calbindin and were the target of enkephalinergic inputs; they possessed somatic spines. These data demonstrate: (1) that the guinea-pig lateral septum contains subpopulations of calbindin neurons which are postsynaptic to enkephalinergic inputs; (2) that Ca2+ conductances are not related to the presence of calbindin; (3) that somatospiny neurons, which are involved in the regulation of the hippocampo-septo-hypothalamic complex, contain calbindin and are the target of enkephalinergic endings.