A transposon-inserted mutant of Drosophila melanogaster was recently identified, and the larvae show no food preference (Ryuda and Hayakawa, 2005). To reveal the genetic mechanism underlying the preference change in this mutant, a large-scale oligo-DNA microarray screening was carried out to identify genes whose expression is different in control and mutant strains. We focused especially on hunger-driven changes in gene expression in the larval central nervous system (CNS) of both strains, because the state of food depletion should promote a feeding response due to changed expression of certain genes in the CNS. We identified 22 genes whose expression changed after starvation in either or both of the two strains. Quantitative RT-PCR analyses confirmed the expression changes in four genes, CG6271, CG6277, CG7953, and new glue 3 (ng3, encoding a putative structural molecule). CG6271 and CG6277 encode triacylglycerol lipase, and CG7953 produces a protein homologous to a juvenile hormone (JH) binding protein. The expression of these two groups of genes was enhanced in control strain larvae with a normal food preference but not in GS1189 strain larvae. Given that these genes contribute to mediating hunger-driven changes in food preference and intake in D. melanogaster larvae, the dysfunction of these key genes could cause the defect in food preference observed in GS1189-strain larvae.