Glycol ethers such as ethylene glycol monomethyl ether (EGME) are common solvents used in many industrial products. A large number of individuals are exposed to EGME through different exposure routes. We investigated the differential distribution of EGME following various routes of administration using whole body autoradiographic (WBA) techniques. Male B6C3F1 mice were treated with tracer iv or oral doses of [2-14C]EGME (4.05 micrograms EGME/kg equivalent to 0.8 mCi/kg) and euthanized at 1 and 24 hr following treatment. In both groups of animals the highest levels of radioactivity were detected in the liver, urinary bladder, bone marrow, kidney, and epididymis, at 1- and 24-hr time periods. Computer-assisted quantitation of WBA indicated that there was markedly higher deposition of [2-14C]EGME and/or its metabolites in various tissues of the orally treated animals than in animals treated intravenously. Our studies also suggest that [2-14C]EGME is rapidly distributed either from blood or stomach to various tissues. Preferential deposition of radioactivity in the peripheral tissues of the bone, with a progressive inward accumulation in the bone marrow, was observed. Selective permeability of EGME and/or its metabolites was indicated by the higher uptake by the epididymis than that by testis. The high levels of radioactivity in biosynthetically active tissues, e.g., the liver, bone marrow, and gastric mucosa, is an indication of persistent interaction of the compound with cellular components of these tissues. These interactions may lead to EGME toxicity.