We have characterized gene expression changes in the midgut tissue of Culex nigripalpus Theobold (Diptera: Culicidae) females, after they ingest a bloodmeal, by differential display of RNA isolated from pre- and postfeeding females. Seventy-two cDNA fragments exhibiting reproducible differences were observed. Of these, 22 showed an increase in gene expression and 50 showed a decrease in gene expression as a result of blood feeding. Eleven cDNA fragments exhibiting increased expression after a bloodmeal were cloned and sequenced. Seven of these were novel transcripts, and they did not match any sequences in GenBank. Three clones were similar to conserved proteins of unknown function from Aedes aegypti (L.) and Anopheles gambiae Giles. Here, we present the expression data on the first cDNA clones isolated from Cx. nigripalpus midgut tissue, including their molecular characterization, and we discuss their possible involvement in blood-feeding–associated processes and disease transmission.