Eleven spectral vegetation indices that emphasize foliar plant pigments were calculated using airborne hyperspectral imagery and evaluated in 2004 and 2005 for their ability to detect experimental plots of corn manually inoculated with Ostrinia nubilalis (Hübner) neonate larvae. Manual inoculations were timed to simulate infestation of corn, Zea mays L., by first and second flights of adult O. nubilalis. The ability of spectral vegetation indices to detect O. nubilalis-inoculated plots improved as the growing season progressed, with multiple spectral vegetation indices able to identify infested plots in late August and early September. Our findings also indicate that for detecting O. nubilalis-related plant stress in corn, spectral vegetation indices targeting carotenoid and anthocyanin pigments are not as effective as those targeting chlorophyll. Analysis of image data suggests that feeding and stem boring by O. nubilalis larvae may increase the rate of plant senescence causing detectable differences in plant biomass and vigor when compared with control plots. Further, we identified an approximate time frame of 5–6 wk postinoculation, when spectral differences of manually inoculated “second” generation O. nubilalis plots seem to peak.