Autistic children undergoing therapeutic programs, which adopt in our service (USL 3 CT) different theoretical approaches, sometimes show a marked reduction in motor activities, a lowering of tone of voice, physical expression of sadness. We observe that animation is absent in the scene they may draw and colours are no longer used in their drawings. Sleep disturbance may appear or reappearance of enuresis. Many authors consider these symptoms as signs of depression. These changes, even though they create new problems in therapeutic management, are, in our opinion, a very important index of the unblocking of autistic withdrawal and beginning of development of those emotional, relational and cognitive components which seem to be frozen in autistic children and inhibit the birth of the mind, according to the U. Frith Theory. We report in this paper the psychoanalytic, cognitive, systemic, biological viewpoint on the occurrence of depression in infantile autism. We submit three cases of patients being treated in our service with the cognitive-behavioural oriented educational program and pharmacological therapy and discuss the multidimensional approach. The temporary occurrence of depression symptoms may be an index of a change within the resisting autistic balance, which may have a biological basis, but indicates the disorganization of the autistic child's mind in view of further development.