Two seemingly contradictory tendencies have accompanied the development of the natural sciences in the past 150 years. On the one hand, the natural sciences have been instrumental in effecting a thoroughgoing transformation of social structures and have made a permanent impact on the conceptual world of human beings. This historical period has, on the other hand, also brought to light the merely hypothetical validity of scientific knowledge. As late as the middle of the 19th century the truth-pathos in the natural sciences was still unbroken. Yet in the succeeding years these claims to certain knowledge underwent a fundamental crisis. For scientists today, of course, the fact that their knowledge can possess only relative validity is a matter of self-evidence. – The present analysis investigates the early phase of this fundamental change in the concept of science through an examination of Hermann von Helmholtz's conception of science and his mechanistic interpretation of nature. Helmholtz (1821-1894) was one of the most important natural scientists in Germany. The development of this thought offers an impressive but, until now, relatively little considered report from the field of the experimental sciences chronicling the erosion of certainty. – Introduction. – A. Mechanism between the Classical and the Modern. I. The Concept of Mechanism : 1. What is Meant by "Mechanism"?; 2. On the Concept of Classical Mechanics; – II. Mechanism as a Classical Philosophy of Nature : 1. The Classical Concept of Science; 2. Two Instances of the Legitimation of Classical Mechanism, a) Galileo's Scientism, b) Descartes' Metaphysics and his Concept of Hypothesis; – III. The Three Lines of Traditions of Mechanism : 1. Materialist Mechanism (Boyle and Huygens); 2. Dualist Mechanism (Newton and Boscovich); 3. Dynamic Mechanism (Leibniz and Kant); – IV. Contours of a Modern Philosophy of Nature : 1. Hypotheticity as a Characteristic of the Modern Conception of Science; 2. Interpretation of Nature as World-View. – B. Helmholtz's Mechanism at the Dawn of Modernity. I. Helmholtz as Educator, Natural Scientist, and Research Strategist. – II. Helmholtz's Classical Mechanism : 1. The Mechanistic Programmatic of 1847, a) The Grounding of Dual Mechanism, b) The Energetic Heuristic of Mechanism; 2. Mechanics as Foundation of Geometry; 3. Helmholtz's Classical Conception of Science and Nature, a) His Conception of Science Until the End of the Eighteen Sixties, b) His Classical Mechanistic Conception of Nature. – III. The Hypothesization of Helmholtz's Mechanism : 1. Helmholtz's Conception of Science Since the Beginning of the Eighteen Seventies; 2. Helmholtz's Model-Theoretical Mechanism. Mechanistic Analogies and Mathematical Unification. – IV. Conditions and Causes of the Change in Helmholtz's Conception of Nature and Science. M.-M. V.