Ethylene glycol monomethyl (EGM) and monoethyl (EGE) ethers were administered po to rats at dosages varying from 50 to 500 mg/kg body weight/day for EGM and 250 to 1000 mg/kg body weight/day EGE for 11 days. First evidence of testicular damage following EGM treatment was observed 24 hr after a single dose of 100 mg/kg body weight when the lesion appeared localized in the primary spermatocyte. At 16 hr after a single dose of 500 mg/kg, mitochondrial damage was one of the first subcellular changes to be demonstrated. Treatment of animals with EGE resulted in a similar lesion; however, to obtain damage of equivalent severity, a larger dosage for a longer period was required. In limited studies with 2-methoxy- and 2-ethoxyacetic acids (putative metabolites of EGM and EGE, respectively), using equimolar doses to their parent compounds (500 mg EGM or EGE/kg for 4 or 11 days, respectively) gave damage of equivalent severity to the corresponding glycol ether. After dosing animals with 500 mg EGM/kg body weight for 4 days, the testes recovered weight, and the majority of tubules recovered their spermatogenic potential within one full maturation cycle. The recovery study also indicated a possible effect on the spermatogonia in a small number of tubules although no morphological abnormalities to this cell type could be observed. No effect levels over the 11-day treatment period were 50 and 250 mg/kg body weight/day for EGM and EGE, respectively.