Multi-barrelled micro-electrode has been used to observe further the effect of Li+ applied iontophoretically on electrical activities of pain related neurons (PRN) of the rat caudate-putamen nucleus (CPN) and its mechanism of action was studied at the cellular level. It was found that PRN were homogeneously distributed throughout the head of CPN, but pain-excitation neurons (PEN) and pain-inhibition neurons (PIN) were heterogeneously distributed. The PIN were mainly distributed in the anterior part, while the PEN primarily in the central part of the head of CPN. The results may provide a clue to understand the complicacy in the pain regulation mechanism undergoing in the head of CPN. Li+ iontophoresis could inhibit the discharges of PEN, while the discharges of PIN were activated. The interference modes of pain discharge of PEN and PIN induced by Li+ iontophoresis were positively related to that induced by morphine. It was suggested that there existed some similarity in the mechanisms of analgesia induced by Li+ and morphine. This, in turn, appears to support the suggestion that endogenous opioid peptides and opioid receptors may be involved in the analgesic effect of Li+.