AbstractThis study establishes that the liver catalase depression in Friend virus‐infected mice is caused by a spleen‐elaborated humoral factor which is not related to bacterial products. This was shown in experiments in Friend virus‐infected germfree mice in which splenectomy resulted in return of liver catalase levels to near‐normal values. The liver catalase‐depressing factor is shown to be a true toxohormone in that it induces thymic involution when injected into healthy mice and fails to inhibit the activity of a liver catalase preparationin vitro.These findings are briefly discussed in connection with work in which ‘toxohormone‐like’ substances have been isolated from nontumor sources. Further experimentation is suggested which may help to decide whether or not true toxohormones are unique