In past studies we have shown that novel 33-kD cysteine protease (Mir1-CP) accumulates in the whorls of maize inbred lines that are resistant to feeding by fall armyworm (Spodoptera frugiperda, FAW) and other Lepidoptera. We have shown that the peritrophic matrix (PM) of larvae that feed on plant material expressing Mir1-CP was damaged and treatment of isolated PMs with purified recombinant Mir1-CP increased PM permeability in a concentration dependent manner. This study was conducted to determine if there are synergistic effects between Mir1-CP and Bacillus thuringensis (Bt-Cry-IIA) toxin on second instar FAW, southwestern corn borer (Diatraea grandiosella, SWCB), Tobacco budworm (Heliothis verisense, TBW) and corn ear worm (Helicoverpa zea, CEW) larval growth. All four larvae reared on control artificial diet had average relative growth rate (RGR) of 0.624± 0.054. However, RGR values for FAW larvae was reduced to 0.1 + 0.054 at combined sublethal concentrations of 60 ng/ml Mir1-CP and 0.4 µg/ml Bt-CryIIA and showed higher percentage mortality than under individual treatment conditions. Both CEW and TBW showed reduced RGR values of 0.07 + 0.01 and 0.09 + 0.03 at combined concentrations of 60 ng/ml Mir1-CP and 0.5 µg/ml Bt-CryIIA. SWCB larvae required a slightly higher Bt-CryIIA concentration of 1 µg/ml to achieve similar synergistic RGR value of 0.05 + 0.01. The synergistic study shows that, stacking of Mir1-CP and Bt-CryIIA in transgenic plants would be good strategy for providing increased resistance against lepidopteran pests