The tropical staple cassava is subject to several major diseases, such as cassava bacterial blight, caused by Xanthomonas axonopodis pv. manihotis. Disease-resistant genotypes afford the only practical solution, yet despite the global importance of this crop, little is known about its defence mechanisms. cDNA-AFLP was used to isolate cassava genes differentially expressed during the hypersensitive reaction (HR) of leaves in response to an incompatible Pseudomonas syringae pathovar. Seventy-eight transcript-derived fragments (TDFs) showing differential expression (c. 75% up-regulated, 25% down-regulated) were identified. Many encoded putative homologues of known defence-related genes involved in signalling (e.g. calcium transport and binding, ACC oxidases and a WRKY transcription factor), cell wall strengthening (e.g. cinnamoyl coenzyme A reductase and peroxidase), programmed cell death (e.g. proteases, 26S proteosome), antimicrobial activity (e.g. proteases and β-1,3-glucanases) and the production of antimicrobial compounds (e.g. DAHP synthase and cytochrome P450s). Full-length cDNAs including a probable matrix metalloprotease and a WRKY transcription factor were isolated from six TDFs. RT-PCR or Northern blot analysis showed HR-induced TDFs were maximally expressed at 24 h, although some were produced by 6 h; some were induced, albeit more slowly, in response to wounding. This work begins to reveal potential defence-related genes of this understudied, major crop.