In 1953 we embarked on an experimental program to test the general hypothesis that variation in brain chemistry is a major determinant of the variation in adaptive behavior among normal individuals. The experimental animal was the rat, the biochemical measure first employed was cholinesterase (ChE) activity, and the adaptive behavior initially studied was "hypothesis preference" as previously defined by Krechevsky (1932).This program was initiated with a specific experimental hypothesis to be tested. Our first completed experiment indicated that this hypothesis was not tenable, but it did suggest that a revision of the original hypothesis could accommodate the data. This revision (our second experimental hypothesis) was then tested in a series of experiments, some of whose results supported the second hypothesis, while others were more ambiguous in their implications. A long-term genetic experiment had meanwhile been started with the hope that it would provide crucial information concerning the tenability of our second hypothesis. This experi-