The article addresses the pattern of vertical distribution of the major long-lived man-made radionuclides 137Cs, 241Am, 90Sr and 239+240Pu in soils of the Semipalatinsk Test Site. Areas of different contamination with radionuclides are discussed – places of aboveground nuclear and fusion tests conducted at the ‘Experimental Field’ site, the fallout in the form of plumes within the Semipalatinsk Test Site, areas of radiological warfare agent tests at the ‘4А’ site, areas of meadow ecosystems associated with radioactively contaminated water streams from test adits of the ‘Degelen’ testing site, conventionally ‘background’ areas of the test site, in which no nuclear or fusion tests were conducted. In the course of research, differences were revealed in the vertical distribution of radionuclides of interest in soils of the above areas. Differences are attributed to the pattern of how contamination with radionuclides is formed and to abiotic and biotic factors such as physical and chemical soil properties, moistening conditions, human activity and others. Based upon findings, recommendations were developed, aimed at the optimization of research into the vertical distribution of radionuclides in the soil cover of the former Semipalatinsk test Site. In particular, it was found that when undertaking such research, it was sufficient to confine oneself to dividing a territory by the soil type and restrict the research depth to 30 cm.