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This article explores the psychical expression of autoimmunity in the analytic situation; it is informed by biological theories of autoimmunity in contemporary immunology. Several of my patients developed autoimmune conditions in the course of their analyses, leading me to consider the role of psychical change in disrupting one’s somatopsychic equilibrium. In the psychoanalytic literature, autoimmunity is used metaphorically for attack against what is foreign or unwanted in ourselves. Contemporary immunology, however, suggests a somewhat different metaphor. “Self-reactive” cells present in the body may attack self unless suppressed by inhibitory mechanisms. Biologically, limited self-destructiveness is necessary, but in autoimmune disease it becomes excessive and pathological. I suggest that the presence of biological “self-reactivity” implies an inherent self-destructiveness in line with Freud’s thinking on the death instinct; the notion that this self-destructiveness also has adaptive aspects may contribute to our understanding of Freud’s ideas. In three vignettes I illustrate clinical application of a modified metaphor of autoimmunity, finding that not only is the fusion of life and death instincts important for psychic development, but so is defusion when contained within the analytic relationship. The analytic task is to restore the balance between constructive and pathological self-destructiveness. Implications regarding controversies in psychosomatic theory are briefly considered.