The emergence and spread of anthelmintic resistance is a serious threat to the sustainability of the livestock industry, particularly the sheep sector. Mechanisms of resistance and the means by which resistant parasites survive anthelmintic treatment are still poorly understood, however differential gene expression may be implicated. In this study, we have investigated the transcriptomic response of a triple-resistant isolate of Teladorsagia circumcincta to ivermectin exposure in vitro, using "next generation" sequencing technology. The study generated ~100,000 new EST sequences, ~50,000 each from both the ivermectin-exposed and -unexposed pools of parasites. Bioinformatic analysis of the expression profiles revealed statistically significant differences in the mean expression levels of four KEGG orthologous groups; 'translation' (P < 0.001), 'amino acid metabolism' (P = 0.001), 'carbohydrate metabolism' (P = 0.022) and 'xenobiotic degradation and metabolism' (P = 0.042). There were also statistically significant differences, within clusters, between the mean expression levels of transcripts from exposed and unexposed worms. Candidate resistance genes such as p-glycoproteins and cytochrome P450s were poorly represented in both datasets. The current study shows that this triple-resistant isolate is affected, at the transcriptome level, by ivermectin exposure and illustrates the potential of next generation sequencing technologies to investigate gene expression and anthelmintic resistance in complex multicellular helminth parasites such as T. circumcincta.