This study was undertaken to evaluate the oncogenicity of inhaled propylene glycol monomethyl ether (PGME) in mice and chronito PGME-induced adaptive changes in liver tissue. Groups of 50 male and 50 female B6C3FI mice per sex per concentration were exposed to targeted vapor concentrations of 0, 300, 1000 or 3000 ppm PGME under dynamic airflow conditions 6 hours/day, 5 days/week, for up to 2 years. Parameters evaluated included: general appearance and demeanor of animals, survival, in-life body weights and weight gains, hematological parameters, selected organ weights, gross and microscopic pathologic changes and tumor incidence. In addition, hepatocellular proliferation rates (at all concentrations) and the activities of selected hepatic mixed function oxygenases (MFO) (at 0 and 3000 ppm) were measured in satellite groups of mice exposed to PGME vapor for 6, 12 or 18 months. No treatment-related increases in tumors were observed in any tissue of male or female mice inhaling PGME vapors. Inhaled PGME, however, did cause several treatment-related nonneoplastic effects, many of which were consistent with metabolic adaptation. While greater than 66% of control and treated mice alike survived the 2-year exposure regimen, mortality of high dose group males was increased relative to controls (34% vs. 18%). A transient sedation of mice inhaling 3000 ppm PGME during the first week of exposures was observed; however, this resolved during the second week of exposures concomitant with adaptive changes in the livers of these animals (previous study results). Mice exposed to 3000 ppm PGME had statistically-identified decreases in mean in-life body weights (2-7%) and body weight gains (5-24%) relative to controls over much of the dosing period. Statistically-identified decreases in in-life body weights were also noted, though less frequently, in both sexes exposed to 1000 ppm PGME vapor. Absolute and relative liver weights and hepatic MFO activity of high exposure group males and females were minimally increased at all or nearly all time periods examined. No treatment-related histopathological changes accompanied these liver effects, nor were histopathological changes noted in any other tissues. These data, along with the occurrence of chronic, albeit small, increases in hepatocellular proliferation in mice inhaling 3000 ppm PGME vapor suggested a minimal regenerative response in liver, likely related to a shortened life span of metabolically- stressed hepatocytes. Based upon the slight depression in body weights of intermediate exposure group mice, the no-observable-adverse-effect level (NOABL) for male and female B6C3FI mice was 1000 ppm PGME.