The protective and therapeutic effects of the H1–antihistamine chlorpheniramine against an acute poisoning induced by organophosphorus insecticide dichlorvos in a 7–14 days old chicks model were evaluated and compared with that of the standard antidote atropine. Chlorpheniramine or atropine at 20 mg/kg, intramuscularly (i.m.) given immediately after oral dichlorvos dosing increased the LD50 value of dichlorvos (10.85 mg/kg, orally) in the chicks by 77 and 123 %, respectively. Chlorpheniramine at 20 mg/kg, i.m. given immediately after dichlorvos (12 mg/kg, orally) significantly delayed the onset of acute signs, time of death, decreased toxicity score and increased the percentages of survivors (62.5 %) during 2 and 24 h after dichlorvos dosing. The antidotal effect of chlorpheniramine and atropine groups at a dose of 20 mg/kg, i.m. given immediately after oral dichlorvos were close to each other in delaying the onset signs of poisoning and time of death. They also significantly increased the percentages of survivors and decreased of toxicity scores. Chlorpheniramine at 20 mg/kg, i.m. significantly decreased plasma (34%) and brain (52%) cholinesterase activities in comparison with the control group. Dichlorvos dosing at 8 mg/kg, orally significantly reduced plasma (83%) and brain (93%) cholinesterase activities in comparison with the control and chlorpheniramine groups. Chlorpheniramine given after dichlorvos dosing significantly protected the plasma and brain cholinesterase from further decreased in its activities caused by dichlorvos dosing by 29 and 41%, respectively. In conclusion, the study suggests that chlorpheniramine have a protective and therapeutic effects in case of dichlorvos poisoning in chicks resembling that of atropine.