The destruction of obsolete larval tissues at the onset of insect metamorphosis is a complex process triggered by the steroid hormone ecdysone. Among the genes required for the implementation of salivary gland (SG) degeneration the reduced bristles on palpus (rbp) gene of the Broad-Complex (BR-C) locus plays a critical role. This gene encodes the BR-C Z1 transcription factor and its expression is directly regulated by ecdysone through the ecdysone receptor (EcR/Usp). The BR-C locus encodes four major protein isoforms, including BR-C Z1, Z2, Z3, and Z4. With the exceptions of mutations in BR-C ZI all mutations affecting the other BR-C isoforms produce pupal lethality. To gain insight into the function of the different BR-C isoforms on the process of SG degeneration, we used transgenes expressing each of the four major BR-C isoform proteins. This study revealed that, depending upon the period of expression relative to the major peak of ecdysone production, BR-C Z1, Z2, and Z4 first inhibited and then stimulated the process of SG degeneration. In contrast, BR-C Z3 exerted all time points an inhibition on SG degeneration. (C) 2002 Elsevier Science (USA). All rights reserved.