The genetics of two highly active esterases, A3H and B3H, in a methyl parathion-resistant strain (MP-R) of Culex tarsalis was investigated in relation to organophosphate (OP) resistance. The increased activity of esterase A3 and of esterase B3 is under the control of two distinct and closely linked (approximately 4.4 centimorgans) genes. Each gene possesses two forms, one controlling high activity (A3H or B3H, respectively) and one controlling low activity (A3L or B3L, respectively) of the enzymes. Organophosphate resistance in the MP-R strain is strongly associated with the presence of these highly active esterases. The results are discussed in relation to the present knowledge on the mechanisms responsible for high activity of esterases observed in other OP-resistant mosquitoes of the genus Culex.