Crystal (Cry) proteins derived from Bacillus thuringiensis (Bt) have been widely used as a method of insect pest management for several decades. In recent years, a transgenic corn expressing the Cry3Bb1 toxin has been successfully used for protection against corn rootworm larvae (genus Diabrotica). The biological action of the Bt toxin in corn rootworms has not yet been clearly defined. Because development of resistance to Bt by corn rootworms will have huge economic and ecological costs, insight into larval response to Bt toxin is highly desirable. We identified 19 unique transcripts that are differentially expressed in D. virgifera virgifera larvae reared on corn transgenic for Cry3Bb1. Putative identities of these genes were consistent with impacts on metabolism and development. Analysis of highly modulated transcripts resulted in the characterization of genes coding for a member of a cysteine-rich secretory protein family and a glutamine-rich membrane protein. A third gene that was isolated encodes a nondescript 132 amino acid protein while a fourth highly modulated transcript could not be further characterized. Expression patterns of these four genes were strikingly different between susceptible and resistant western corn rootworm populations. These genes may provide useful targets for monitoring of Bt exposure patterns and resistance development in pest and non-target insect populations.