Dosing male mice with 125 mg dichlorvos/kg orally produced cholinergic overstimulation and death in up to 100% of the animals. Administration of 20 or 30 mg diphenhydramine HCl/kg s.c. 15 min before dichlorvos dosing significantly reduced the development of toxicity and increased 24-h survival rates to 87 and 100% respectively. Diphenhydramine was less effective when given immediately after dichlorvos dosing; however, repetitive treatments of 20 mg diphenhydramine/kg s.c. increased the survival rate to 75%. The administration of a single injection of 30 mg diphenhydramine/kg s.c. 15 min before dichlorvos dosing or as multiple s.c. or i.p. doses after dichlorvos increased the 24-h oral dichlorvos LD50 by 30, 50 or 70%, respectively. The anticholinergic effects of diphenhydramine protects and effectively treats mice poisoned with dichlorvos.