The object of this paper is to trace the growth of a fundamental problem that for a decade hindered the development of several lines of muscle research: the molecular mechanism that allows and controls contraction and relaxation of muscle fiber. Emphasis is placed on the difficulties to be overcome; thus the paper records not only the achievements and successes, but also the unavoidable failure and disappointments. The account highlights the essential contribution of Setsuro Ebashi to find the solution of the problem. (c) 2007 Elsevier Inc. All rights reserved.