For much of the 20th century scientific psychology treated the relative contributions of nature and nurture to the development of phenotypes as the result of two quite separate sources of influence. One, nature, was linked to biological perspectives, often manifest as ''instinct'', while the other, nurture, was taken to reflect psychological influences. We argue that this separation was contingent on historical circumstance. Prior to about 1920, several perspectives in biology and psychology promoted the synthesis of nature and nurture. But between 1930 and 1980 that synthetic consensus was lost in America as numerous influences converged to promote a view that identified psychological and biological aspects of mind and behavior as inherently separate. Around 1960, during the hegemony of behaviorism, Daniel Lehrman, Gilbert Gottlieb, and other pioneers of developmental psychobiology developed probabilistic epigenesis to reject predeterminist notions of instinct and restore a synthesis. We describe the earlier and later periods of synthesis and discuss several influences that led to the separation of nature and nurture in the middle of the 20th century. ß 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 758-769, 2007.