A number of major pharmacological actions of homofenazine were tested with animals in comparison with those of chlorpromazine {CPZ) and physiological saline. .Many common pharmacological properties were found between homofenazine and CPZ but in most of the cases, the drug action was stronger with CPZ than with homofenazine. However, some important differences were also observed. For example, at high doses of CPZ mice showed irritability or aggressiveness which was not observed with homofenazine. Similarly CPZ-treated cats were more excited than homofenazine-treated cats although the latter drug was injected twice as much as the former. Secondly, homofenazine reduced amount of spontaneous activity in mice as a function of dose level, but no such dose-response relationship was found with CPZ. In addition, homofenazine produced a stronger antagonism against the amphetamine-induced activity level in mice than did CPZ. Thirdly, CPZ had a stronger detrimental action upon motor coordination than homofenazine in mice. Fourth, no obvious detrimental effect was found with homofenazine upon shock-motivated running responses in rats, while the effect appeared with CPZ, although homofenazine like CPZ inhibited the avoidance response. In conclusion, the present findings were in general accordance with previous clinical studies (Bente & von Schlichtegroll, 1964; Greif & Liertzer, 1965; Itil, 1965) in that homofenazine had a potent sedative and tranquilizing effect as CPZ although autonomic and ataxic effects were less effective with homofenazine than with CPZ.