Introduction: Organophosphate compounds (OPs) are potent and effective insecticides widely used in human practice. They are irreversible cholinesterase inhibitors causing accumulation of acetylcholine at cholinergic synapses with over-stimulation of muscarinic and nicotinic receptors. In Egypt, little is known about susceptibility to toxic effects of OPs during pesticide application. Aim of work: To study the genetic variation in Butyrylcholine esterase (BChE) among workers presented to the National Egyptian Centre of Toxicological and Environmental Research (NECTR) with acute toxicity during spraying of organophosphorus pesticide and having occupational history of chronic exposure. Materials and methods: It is a case–control study to assess BChE genotype and enzyme activity in 65 workers presented to NECTR at Cairo, Egypt, during the period from January 2014 to July 2016. Comparison with 55 matched control subjects was performed; to identify those workers at risk to potential adverse health effects of OP compounds. The studied group answered a predesigned questionnaire with detailed personal medical and occupational histories. Full physical examination was done. Laboratory investigations included: liver and kidney functions, analysis of pseudo choline esterase and DNA. Results: The study revealed that 73.8 % of the total cases was carrying JK variants (named in honor of James and Kalow respectively) in heterozygote state with the A (Atypical) variant an d 13.8 %in heterozygote state with the U (Usual) variant, these workers showed reduction in the level of BChE enzyme . Conclusion: BChE genetic variations could be a concern in farm workers exposed to organophosphorus pesticides in agriculture and could be useful in assessing the risk of pesticide exposure. Safety regulations concerning products use, training of occupational workers for the safe application of potentially harmful pesticides are highly recommended.