On the basis of our present knowledge of organophosphorus resistance in the house fly (Musca domestica L.) we are in a good position to plan and undertake directed research to progress toward solutions to this problem even while more basic and fundamental information is being accumulated. Two possible lines of research which merit high priorities are as follows: one is the development of synergists for organophosphorus insecticides, and a second is the development of compounds which are active cholinesterase inhibitors but whose structural Configurations are unacceptable to the detoxication enzymes or at least much less acceptable than those of the organophosphorus insecticides to which resistance has developed.

The evidence at hand suggests that organophosphorus resistance is biochemically limited and relatively unstable. It does not exhibit a group resistance pattern as does chlorinated-hydrocarbon resistance. The organophosphorus resistance mechanism is not primarily concerned with the toxic action mechanisms of the mode of action of organophosphorus compounds but is related to detoxication mechanisms and the rate of destruction of the active compound in relation to the rate of accumulation in critical concentration at sites of action. The structural configurations of organophosphorus compounds required for effectiveness in the intoxication systems are not identical with those required for the detoxication systems. The relationship between chemical structure and resistance is based on the fine structure of organophosphorus compounds, not on their gross structure. Organophosphorus resistance primarily involves certain closely related enzymes which are capable of detoxifying only limited spectra of structurally related organophosphorus insecticides, and changes in substrate specificity are accomplished at the expense of effective activity toward previous substrates. It therefore seems possible that a particular resistant. strain may he highly resistant at any one time to only a limited spectrum of organophosphorus insecticides and may then always be susceptible to a portion of those available.