Deca-bromo-diphenyl ether (DBDE) is one of the most efficient brominated flame retardant (BFR) available on the market. We recently demonstrated that when administered to female rat by oral route, DBDE is efficiently absorbed, with the highest residual concentrations found in two endocrine glands, namely the adrenal glands and the ovaries. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging, a technique usually used for the study of endogenous compounds, was applied for the first time to a persistent organic pollutant, allowing to detect and to precisely localize DBDE residues in these two target tissues. The detection of the bromide ion ((81)Br isotope) by TOF-SIMS mass spectrometry imaging allowed us to demonstrate a marked cortical tropism of DBDE residues for the adrenal glands in female rats dosed per os 2 mg·kg(-1) DBDE, daily, over 96 h. In ovaries, DBDE residues were found to be concentrated in spots corresponding to part of the corpora lutea. Hepatic residues of DBDE were found to be homogeneously distributed. Due to the intrinsic toxicity of DBDE, its accumulation in the adrenal glands and the ovaries may be connected to the mechanisms of actions by which DBDE could trigger endocrine disruption in mammals.