ICI-63197 is a potent and selective phosphodiesterase IV (PDE 4) inhibitor with potent antidepressant activity. The antidepressant action of ICI-63197 realizes via enhancement of central noradrenergic transmission due to selective inhibition of cAMP phosphodiesterase. ICI 63 197 was investigated in mice for its effectiveness in two classical test models for prediction of clinical antidepressant activity: antagonism of reserpine-induced hypothermia or hypokinesia and potentiation of yohimbine lethality. ICI 63 197 was approximately 15 times more potent than imipramine in antagonizing reserpine-induced hypothermia. The antihypothermic effect of the ICI-63197 occurred at a smaller dose than that of imipramine. In contrast to imipramine, the ICI-63197 reversed reserpine-induced hypokinesia. ICI-63197 approximately, as potent as imipramine in potentiating the lethality of yohimbine. ICI 63 197 was never tested in clinical trials.