The aim of this study was to investigate the genotoxic effect on the peripheral blood lymphocytes potentially induced by yttrium-90 citrate colloid (Y-90) in children who were undergoing radiosynovectomy for hemophilic synovitis, using chromosomal aberration analysis (CA) and the micronuclei (MN) assay for detecting chromosomal aberrations, as well as the sister chromatid exchanges (SCE) technique for assessed DNA damage. Materials and Methods: Cytogenetic analyses were undertaken in 18 boys (mean age, 14.5 +/- 2.1 years) with hemophilic synovitis who underwent radiosynovectomy with Y-90. CA, MN, and SCE were evaluated just prior to, then at 2 and 90 days following radiosynovectomy from the peripheral lymphocytes of the children. An activity of 185 MBq of Y-90 was injected into the 18 knee joints under aseptic conditions. To check the possibility of leakage from the joint and its migration within the body, the patients underwent scanning under a dual-headed gamma camera at the hours 2 and 48 following the procedure. Results: The procedure was well tolerated in all the children, and there was no extra-articular activity owing to extraarticular leakage of radioactive material in whole-body imaging. The mean frequency of CA in lymphocytes determined prior to the onset of therapy (0.31 +/- 0.48/900 cells) was not significantly increased, in comparison to the control values obtained 2 (0.30 +/- 0.48/900 cells) and 90 days (0.15 +/- 0.37/900 cells) after radiosynovectomy (p = 1.0 and 0.625, respectively). We observed that MN frequency was mildly increased in lymphocytes 2 days after therapy (8.30 +/- 1.89 MN/1000 binucleated cells vs. 9.23 +/- 1.79 MN/1000 binucleated cells; p = 0.013). But there was no significant difference between the baseline and the day 90 control levels of MN (p = 0.196). In the analysis of SCE frequency, there were no significant differences between the baseline (8.11 +/- 0.77) and the control analysis performed 2 and 90 days following radiosynovectomy (8.18 +/- 0.77 and 8.07 +/- 0.74; p = 0.710 and 0.662, respectively). Conclusions: The results of this study indicated that high radiation doses are not obtained by peripheral lymphocytes of children who undergo Y-90 radiosynovectomy and, therefore, they contradict a high cancer risk.