The American Journal of Psychiatry has received a number of letters in re sponse to my earlier "Framework" article (1). Some of these are reprinted else where in this issue, and I have answered them briefly there. However, one issue raised by some letters deserves a more detailed answer, and that relates to whether biology is at all relevant to psychoanaly sis. To my mind, this issue is so central to the future of psychoanalysis that it cannot be ad dressed with a brief comment. I therefore have written this article in an attempt to outlinethe impor tance of biology for the future of psychoanalysis.(Am J Psychiatry 1999; 156:505-524)We must recollect that all of our provisional ideas in psychology will presumably one day be based on an or ganic substructure.-Sigmund Freud, "On Narcissism" (2) The deficiencies in our description would probably vanish if we were already in a position to replace the psychological terms with physiological or chemical ones.… We may expect [physiology and chemistry] to give the most surprising information and we cannot guess what answers it will return in a few dozen years of questions we have put to it. They may be of a kind that will blow away the whole of our artificial structure of hypothesis.-Sigmund Freud, "Beyond the Pleasure Principle" (3) During the first half of the twentieth century, psy choanalysis revolutionized our understanding of men tal life. It provided a remarkable set of new insights about unconscious mental processes, psychic deter minism, infantile sexuality, and, perhaps most impor tant of all, about the irrationality of human motiva tion.