Abstract. Larvae of Helicoverpa armigera (Hübner), a polyphagous lepidopteran crop pest, adapt to the presence of protease inhibitors in their diet by differential regulation of multiple genes encoding digestive proteases. The time-course of their response to dietary soybean Kunitz trypsin inhibitor (SKTI) involves several stages; an initial up-regulation of all protease genes assayed (up to 12 h after exposure to inhibitor) is succeeded by a longer-term down-regulation of expression of specific genes that encode proteases most sensitive to the inhibitor, whereas genes encoding putative inhibitor-insensitive proteases continue to be up-regulated (after 24 h of exposure). Consequently, insect protease activity changes from being sensitive to the inhibitor, to being largely insensitive. The insect response is comparable in its timescale with that of the synthesis of protease inhibitors in the plant wounding response. SKTl causes similar effects on protease gene expression and gut protease activity when fed in diets containing casein or hydrolysed casein as sources of amino acid, suggesting that the insect response is not mediated through inhibition of digestive proteolysis. Soybean Bowman–Birk inhibitor, which has a broader range of inhibitory activity against gut proteases in H. armigera, but is a less effective inhibitor on an I50 basis, proves to be a more effective antimetabolite than SKTI, but does not induce inhibitor-insensitive protease activity because it causes a general up-regulation of protease-encoding genes. A possible mechanism to account for these different responses is discussed.