Genome-wide microarray analysis (Affymetrix array) was used ( i ) to determine whether only one gene, the cytochrome P450 enzyme Cyp6g1 , is differentially transcribed in dichlorodiphenyltrichloroethane (DDT)-resistant vs. -susceptible Drosophila ; and ( ii ) to profile common genes differentially transcribed across a DDT-resistant field isolate [ Rst(2)DDT Wisconsin ] and a laboratory DDT-selected population [ Rst(2)DDT 91-R ]. Statistical analysis (ANOVA model) identified 158 probe sets that were differentially transcribed among Rst(2)DDT 91-R , Rst(2)DDT Wisconsin , and the DDT-susceptible genotype Canton-S ( P < 0.01). The cytochrome P450 Cyp6a2 and the diazepam-binding inhibitor gene ( Dbi ) were over transcribed in the two DDT-resistant genotypes when compared to the wild-type Drosophila , and this difference was significant at the most stringent statistical level, a Bonferroni correction. The list of potential candidates differentially transcribed also includes 63 probe sets for which molecular function ontology annotation of the probe sets did not exist. A total of four genes ( Cyp6a2 , Dbi , Uhg1 , and CG11176 ) were significantly different ( P < 5.6 e -06 ) between Rst(2)DDT 91-R and Canton-S. Additionally, two probe sets encoding Cyp12d1 and Dbi were significantly different between Rst(2)DDT Wisconsin and Canton-S after a Bonferroni correction. Fifty-two probe sets, including those associated with pesticide detoxification, ion transport, signal transduction, RNA transcription, and lipid metabolism, were commonly expressed in both resistant lines but were differentially transcribed in Canton-S. Our results suggest that more than Cyp6g1 is overtranscribed in field and laboratory DDT-resistant genotypes, and the number of commonalities suggests that similar resistance mechanisms may exist between laboratory- and field-selected DDT-resistant fly lines.