The time-course of 5-HT-induced intracellular Ca2+ mobilization in platelets displays biphasic curves; a rapid peak occurs within 10 sec, followed by a prolonged plateau phase. In platelets of patients with affective disorders, many reports have suggested that there is an increase in the rapid peak in intracellular Ca2+ mobilization, but there is no report concerning the plateau phase in intracellular Ca2+ mobilization. We, then, assessed the time course of 5-HT-induced Ca2+ mobilization to compare untreated manic patients with euthymic bipolar disorders and normal subjects. Not only peak amplitude but also plateau phase were more significantly enhanced in the platelets of untreated manic patients than in those of normal controls. These results suggest that the serotonergic neural transmission by means of intracellular Ca2+ was enhanced by the prolonged plateau phase as well as by increased peak amplitude in platelets of mania. The enhanced rapid peak and plateau phase in untreated bipolar mania were restored to their control levels in treated euthymic bipolar disorders. These findings suggest that the reduction of the enhancement in Ca2+ mobilization might be related to either the effects of chronic treatment with lithium or the affective states of the patients.