Male and female C57BL, DBA, and C3H mice were injected intraperitoneally with a single 6.33 mg/kg dose of diisopropylphosphofluoridate (DFP). The time course of recovery of acetylcholinesterase (AChE) activity as well as effects on choline acetyltransferase (ChAT) activity and brain muscarinic and nicotinic receptors were measured. DFP treatment did not affect ChAT activity or the muscarinic and nicotinic receptors. Near control levels of AChE activity were regained in female mice within the first 20 days. However, levels of whole brain AChE activity remained depressed for as long as 40 days following a single dose of DFP in male mice. An analysis of the recovery of AChE activity in several brain regions indicated that control activity was regained in striatum, hindbrain, and hippocampus, but not in cortex, midbrain, and hypothalamus. These data are discussed in terms of potential neurotoxicity induced by a single dose of DFP.