The ability of chronic lithium administration to modify tricylic antidepressant-induced supersensitivity development in cells receiving 5-hydroxytryptamine (5-HT) input was investigated using microiontophoretic techniques. In these experiments, chronic chlorimipramine (or imipramine) administration for a period of 14 days resulted in a 5-fold increase in the sensitivity of hippocampal pyramidal cells to iontophoretically applied 5-HT. This supersensitivity was not blocked by the concurrent administration of lithium. The data suggests that blockade of supersensitivity development by lithium as previously demonstrated in the dopamine system may not be generalized to all central amine systems.