The authors evaluated gene expression in the peripheral blood in relation to occupational exposure in Mayak workers to find out about the existence of a permanent post exposure signature. Workers were exposed to combined incorporated 239Pu and external gamma rays (n = 82) or to external gamma rays only (n = 18), and 50 unexposed individuals served as controls. Peripheral blood was taken from workers older than 70 y. RNA was isolated, converted into cDNA, and stored at −20°C. A two-stage study design was performed focusing on examinations on the transcriptional (mRNA) and post-transcriptional level (microRNA). In the first stage, 40 samples were identified for screening purposes and selection of candidate genes. For examinations on the transcriptional level, whole genome microarrays and qRT-PCR were employed on the post-transcriptional level (667 microRNAs). Candidate genes were assessed by (1) introducing a twofold difference in gene expression over the reference group and (2) showing a significant p-value using the Kruskal-Wallis test. From 42,545 transcripts of the whole genome microarray, 376 candidate genes (80 up-regulated and 296 down-regulated relative to the reference group) were selected. Expression of almost all of these genes (70−98%) appeared significantly associated with internal 239Pu and to a lesser extent were associated with external gamma-ray exposure (2−30%). Associations in the same direction were found for 45 microRNAs. Although both exposures led to modulations of different gene sets in different directions, the authors could detect no differences in gene set enrichment analysis.