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This paper presents research data on water contamination levels of artificial radionuclides and heavy metals in Karabulak Creek at the Semipalatinsk Test Site. The uranium isotopic composition has been studied (²³⁵U and ²³⁸U). Priority contaminants and the most ‘contaminated’ sections of the Karabulak creek were identified, and water quality-related indicators were also estimated. The environmental situation around Karabulak Creek at the «Degelen» site—at which underground nuclear tests have been conducted—was found to be unique and attributed to the combined effect of man-made radiation and natural factors and, in particular, to geochemical features of the region.