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Two quite different cultures are to be found within psychoanalysis, one more clinical in orientation, more focused on meaning and interpretation, and relying primarily on the traditional case study method, the other more research-oriented, focused on cause-and-effect relationships, and relying primarily on methods borrowed from the natural and social sciences. The history of this divide is reviewed and arguments, pro and con, about the potential contributions of specific types of empirical investigation are discussed. Increasingly, it seems, criticisms concerning the scientific status of psychoanalysis are being responded to by empirical research. This has contributed to a growing recognition within the scientific community of the credibility of aspects of psychoanalytic theories and of the effectiveness of psychodynamic treatment. However, some segments of the psychoanalytic community are concerned that this increase in the quantity and quality of empirical research on psychoanalytic concepts risks creating an empirical one-sidedness, while other segments are concerned that not engaging in systematic empirical research can lead to intellectual isolation, fragmentation, stagnation, and orthodoxy. To counter this polarizing tendency, a recommendation is made for methodological pluralism. Adopting this stance could contribute to an enriched understanding of the clinical process and to the development of new research methodologies to investigate complex psychodynamic hypotheses, thus bridging the gap between the two psychoanalytic cultures, as well as the gap between research and clinical practice.