The present studies were undertaken to investigate the differences between the antidepressant drug, imipramine, and liquid nutritive and tonic drugs (NTDs) that consist of Ginseng radix, Epimedii herba, Holen and an additional eight to twelve crude drugs. After preloading forced swimming, the NTD (applied orally, 0.1 ml/10 g) significantly increased the duration time of swimming and decreased the duration time of immobility, while the administration of imipramine (5, 10 and 20 mg/kg, i.p.) under the same conditions and after the same treatment did not produce these positive effects. After pretreatment with 100 mg/kg tetrabenazine, the NTDs also elicited both the increased locomotor activity and the decreased duration time of immobility. The behavioral effect was similar to treatment with imipramine. The NTDs showed a long lasting effect on swimming behavior in the forced swimming test for 15 min, indicating a prolonged efficacy, not like the short effect of imipramine. The present results indicate that the effect of NTDs on fatigued subjects is different from that of imipramine, probably due to involvement of another factor in addition to the antidepressant effect.