The production of antibodies against the organophosphorus hapten soman has been undertaken in vivo in rabbits and in vitro by employing monoclonal techniques. The polyclonal rabbit antibodies did not cross-react with soman but were inhibited by soman analogs in a competitive inhibition enzyme immunoassay ( CIEIA ). In contrast the monoclonal antisoman antibodies were inhibited specifically by soman in the CIEIA but not by sarin nor the hydrolysis products of soman. The monoclonal antibodies were able to compete with acetylcholinesterase (AChE) for soman when the antibody was present in a molar concentration equal to the antibody-soman dissociation constant, resulting in a retardation of the rate of inhibition of AChE by soman. When monoclonal antibodies were administered to mice in a passive immunization regimen, the times-to-death increased twofold at an LD70 or LD90 dose level. These results suggest that the monoclonal antibodies have proper characteristics for use as an immunocytochemical reagent of high specificity. The ability of the antisoman monoclonal antibodies to compete with AChE for soman in vitro and the preliminary in vivo data indicate that selected monoclonal antibodies may prove useful in a therapeutic or prophylactic mode for organophosphorus poisoning.