The influence of adrenocorticotropic hormone (ACTH) and prednisone on the effects of amitriptyline (AMI), imipramine (IMI), mianserin (MIA) or nomifensine (NOM) was investigated in forced swimming and in open field tests. ACTH (50 I.U./kg) or prednisone (1 mg/kg) were given in a single dose or for 7 consecutive days alone or together with AMI (10 mg/kg), IMI (10 mg/kg), MIA (10 mg/kg) or NOM (2 mg/kg). It was found that neither ACTH nor prednisone administered alone in a single dose or for 7 days influenced the behavior of rats. ACTH co-administered with AMI or NOM in a single dose or with AMI, IMI or NOM for 7 days potentiated the antiimmobility effect of antidepressant drugs. Prednisone potentiated only antiimmobility effect of NOM in forced swimming test. ACTH as well as prednisone co-administered with NOM (but not with the other drugs), in a single dose as well as for 7 days, increased also locomotor activity in open field. Neither ACTH nor prednisone influenced the effect of MIA in both tests used. It was concluded that the specific synergism exists only between ACTH and tricyclic antidepressants (AMI, IMI). The observed behavioral interaction between ACTH and AMI or IMI does not seem to be mediated by adrenocorticoids (prednisone was without effect). The potentiation of NOM effects by ACTH as well as by prednisone and lack of any interaction with MIA seems to be related with different mechanism of action of those antidepressant drugs.