Vygotsky s works provide a number of general ideas that form the methodological base of experimental-genetic method. However, more specific principles of organizing and constructing the experimental exploration of the higher mental functions development for the most part remain unclear and undefined. This paper attempts to fill this methodological gap. It describes the main principles underlying genetic research methodology that constitute the methodological base upon which experimental investigations may then be constructed. These principles represent a synthesis of theoretical assumptions, concepts and ideas proposed within the framework of cultural historical theory, and the basic features of the research method. Following these principles in any experimental study on development helps to fulfill two important tasks. First, this creates a unity of object and method, making it possible to experimentally explore the very process of higher mental functions development in such aspects that correspond with the tasks of a particular research. Second, it provides an opportunity to experimentally reveal and capture the differences between organic and cultural processes of development and maturation, between two genetic layers quite different both in their essence and in their nature and, therefore, between two principally different series of patterns that shape these two lines in child development.