This review presents recent evidence of a differentiation in the field of melancholic depression into two subcategories: Highly anxious-retarded depression and depression with above-normal plasma vasopressin (AVP) concentration. This differentiation has been enabled by the use of multidimensional structures of psychopathology, character and temperament, and different vasopressinergic parameters. Melancholia was multi-dimensionally redefined as the highly anxious-retarded subcategory. This subcategory was subsequently validated by relations with the character trait of low Self-Directedness, late remission, correlating vasopressin (AVP) and cortisol concentrations, and a positive family history of depression. The other subcategory, with above-normal plasma AVP concentration, related significantly with familial depression, and was further validated by correlating AVP and cortisol concentrations, the character trait of low Cooperativeness, a state-dependent reduction of the temperament of Reward-Dependence, and correlating anxiety and retardation scores. These data suggest that increased responsivity of the vasopressin V1b receptor is involved in the highly anxiousretarded subcategory, and genetically increased release of AVP, stimulating V1a and V1b receptors, in depression with above-normal plasma AVP. The multilevel and multidimensional clinical description may be useful in other fields of psychiatry. Keywords: Melancholia, anxiety, retardation, social behavior, temperament, character, vasopressin, animal models