Bacteria play important roles in plant-herbivore interactions and communicate with each other with chemical signals, often N-acylhomoserine lactones (AHL). Plant responses to these signals may influence resistance to microbial attack, but the effects of these signals on herbivore defense are unstudied. To determine whether AHL influence jasmonate (JA)-mediated herbivore resistance in Nicotiana attenuata, we treated wild-type (WT) and JA-deficient genotypes (antisense expression of NaLOX3) with N-hexanoyl-dl-homoserine lactone (C6-HSL) and measured the performance of Manduca sexta larvae. Larval mass gain on C6-HSL-treated WT plants was equivalent to that on non-treated NaLOX3-silenced plants, but significantly 4.1-fold larger than on untreated WT plants. Mass gain was unaffected by C6-HSL treatment of NaLOX3-silenced plants. Microarray analysis of the plants elicited with C6-HSL and JA inducing fatty acid-amino acid conjugates revealed a down-regulation of a proteinase inhibitor in the C6-HSL-treated WT plants. The results therefore suggest that the increased performance of M. sexta was due to direct or indirect effect of C6-HSL on JA-mediated defenses.