In addition to its role in the modulation of functions such as arousal and attention, learning and memory, the limbic system has repeatedly been described to be involved in the regulation of several behavioral aspects concerning the adaptation to aversive situations, including pain. A key role in these processes seems to be played by the septo-hippocampal system. This paper, far from being a comprehensive review of all the data available about the limbic system, describes some of the circuits participating in the septo-hippocampal system, with the aim of contributing to an understanding of the sex differences in the behavioral, hormonal and neuronal responses to aversive stimuli. It will appear that the complex anatomical and functional interactions between the different neurotransmitters acting at this level prevent one from indicating a certain substance as more important than others in determining a difference between the two sexes. This leads to the conclusion that the septo-hippocampal formation in tote plays a key role in determining the sex differences in the 'pain experience'. (C) 1997 Elsevier Science B.V.