The LD50 (95% confidence limits) of the organophosphorus insecticide acephate was estimated to be 351, 380, and 321 mg/kg (295–416, 280–516, and 266–388 mg/kg) for CD-1 laboratory mice (Mus musculus), white-footed mice (Peromyscus leucopus noveboracensis), and meadow voles (Microtus pennsylvanicus), respectively. In a second study, these species were provided mash containing 0, 25, 100, and 400 ppm acephate for five days. Brain and plasma cholinesterase activities were reduced in a dose-dependent manner to a similar extent in the three species (inhibition of brain acetyl-cholinesterase averaged for each species ranged from 13 to 22% at 25 ppm, 33 to 42% at 100 ppm, and 56 to 57% at 400 ppm). Mash intake, body or liver weight, plasma enzyme activities (alkaline phosphatase, alanine and aspartate aminotransferase), hepatic enzyme activities (aniline hydroxylase, 7-ethoxycoumarin O-deethylase, and glutathione S-transferase), and cytochrome content (P-450 and b₅) were not affected by acephate ingestion, although values differed among species. In a third experiment, mice and voles received 400 ppm acephate for 5 days followed by untreated food for up to 2 weeks. Mean inhibition of brain acetylcholin-esterase for the three species ranged from 47 to 58% on day 5, but by days 12 and 19, activity had recovered to 66 to 76% and 81 to 88% of concurrent control values. These findings indicate that CD-1 laboratory mice, white-footed mice, and meadow voles are equally sensitive to acephate when maintained under uniform laboratory conditions. Several factors (e.g., behavior, food preference, habitat) could affect routes and degree of exposure in the field, thereby rendering some species of wild rodents ecologically more vulnerable to organophosphorus insecticides.