Few studies concerning the potential genetic effects of diagnostic radionuclides used in nuclear medicine have been reported. The aim of this study was to evaluate the biological and cytogenetic consequences of two technetium 99m-labelled radiopharmaceuticals. Ultrastructural modifications of pulmonary cells were first investigated after injection of 99mTc labelled microspheres in the rat. On the same irradiated cells, nuclear expression of p53 protein was assessed using immunohistochemistry. Despite very high previously calculated doses delivered to pulmonary cells, no morpholological cell damage and no significant increase of nuclear expression of the p53 were noted. There was no correlation between the calculated dose and the ultrastructural biological damage. Secondly, a specific in vitro curve, activity/number of unstable chromosomal aberrations, corresponding to physical characteristics of 99mTc, was established to verify the potentiality of 99mTc to induce such aberrations. In vivo, cytogenetic effects were assessed on blood samples of 5 patients with various arthrosic and periarthrosic diseases obtained after bone scintigraphy. Aberration frequencies of both in vitro and in vivo irradiated lymphocytes were determined using the classical Fluorescence Plus Giemsa technique. No cytogenetic effects appeared with the routinely 99mTc injected activities as predicted by the in vitro curve.