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Lachesis muta mutaand Bothrops atroxsnakes are responsible for most accidents occurring in the Amazon. The clinical features of the accidents are similar; however, there are still controversies about the efficacy of Bothropsantivenoms for treating L. m. mutaaccidents. In this work, we evaluated the antigenic cross-reactivity between these venoms using polyclonal and monoclonal antibodies and the efficacy of B. atroxand L. m. mutaexperimental antivenoms in cross-neutralizing the main toxic activities of each venom. Electrophoretic patterns differed consistently between the species. However, antigenic cross-reactivity was extensive except for a few bands. Several species-specific monoclonal antibodies were obtained by immunization of Balb/c mice with L. m. mutawhole venom or B. atroxand L. m. mutaspecific antigens. The monoclonal antibodies specific to L. m. mutarecognized different bands of this venom and the antibodies specific to B. atroxrecognized a complex pattern on whole venom by Western blotting. These antibodies are important tools for developing an immunoassay able to discriminate patients bitten by these snakes. The experiments involving cross-neutralization of the main activities of the venoms showed that hemorrhage and blood incoagulability induced by B. atroxvenom were similarly neutralized by both B. atroxand L. m. mutaantivenoms. However, B. atroxantivenom partially neutralized the hemorrhage and completely failed in neutralizing coagulopathy induced by L. m. mutavenom. Therefore, antigenic variation between B. atroxand L. m. mutavenoms does occur and the use of specific antivenom is suggested for patients bitten by Lachesissnakes.