Technical Abstract: Nine pharmaceutical inhibitors of eicosanoid biosynthesis (e.g., bromophenacyl bromide, clotrimazole, diclofenamic acid, esculetin, flufenamic acid, domethacin, nimesulide, sulindac, tolfenamic acid) that increased the susceptibility of the gypsy moth, Lymantria dispar (L.), to the nucleopolyhedrovirus LdMNPV were tested against the beet armyworm Spodoptera exigua (Hubner), the corn earworm Helicoverpa zea (Boddie) and the fall armyworm Spodoptera frugiperda (J.E. Smith) and their respective NPVs to determine whether these compounds also alter the susceptibility of these insects. The susceptibility of the beet armyworm was increased by six inhibitors (bromophenacyl bromide, clotrimazole, diclofenic acid, esculetin, flufenamic acid, nimesulide). The susceptibility of the fall armyworm was increased by seven inhibitors, (bromophenacyl bromide, diclofenamic acid, esculetin, indomethacin, nimesulide, sulindac, tolfenamic acid), whereas the susceptibility of the corn earworm was increased by only one inhibitor (sulindac). The influence of the cyclooxygenase inhibitor, indomethacin was expressed in a dose-related manner in beet armyworms. We infer from these findings that eicosanoids, including prostaglandins and lipoxygenase products, act in insect anti-viral defenses.