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In the early 1950’s, during the near avalanche of discoveries, rediscoveries, and redefinitions of subcellular components made possible by electrons micros-copy, those prospecting in this newly opened field were faced with the prob-lem of what to do with their newly acquired wealth. It could be increased by extending the inquiry on the horizontal to many other cell types prepared by many other techniques; it could be extended in further depth, instrumental resolution permitting (“ultra ” was the preferred prefix of the period); or it could be used as a guide to monitor cell fractionation procedures of the type previously developed by Claude (1). The last alternative seemed particularly attractive since the small dimensions of many of the newly discovered structures suggested that they were relatively simple macromolecular as-semblies. At their level, structure- as traditionally envisaged by the micro-scopist- was bound to merge into biochemistry, and biochemistry of mass-isolated subcellular components appeared to be the best way to get at the function of some of the newly discovered structures. The example provided by the work on isolated mitochondria was recent and still shining (2, 3). At the time the structures of interest were the “small particulate component of the cytoplasm ” (4) soon to become in succession “ribonucleoprotein particles ” (5) and “ribosomes ” (6), and the endoplasmic reticulum (ER) originally discovered by Porter, Claude and Fullam (7) and then studied by Porter (8) and by Porter and myself (9-11). Philip Siekevitz joined me in 1955 and together we started a long series of integrated morphological and biochemical studies on the pancreas of the guinea pig using primarily a combination of electron microscopy and cell fractionation procedures. The choice of the pancreatic exocrine cell, a very efficient protein producer, as the object for our studies reflected in part our training, and in part our environment. I was coming from a medical school where I had acquired an interest in “microscopical anatomy ” and “physiological chem-istry ” and great respect for the work of Claude Bernard, Rudolf Heidenhai