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Degradation of the neuropeptide [His(7)]-corazonin, a key hormone in phase transition in locusts was studied using [H-3] [His(7)] -corazonin, RP-HPLC and mass spectrometry. After 4 h incubation, 50 and 75% of [His(7)]-corazonin could still be found in hemolymph of gregarious and solitarious Schistocerca gregaria, respectively. Under in vivo conditions the half-life was 30 min. These results are in contrast to many other neuropeptides that usually have half lives of a few minutes. The peptide is cleaved first by an endopeptidase, either just before or after the Tyr residue at position 5. Next, the C-terminal degradation fragments are further degraded by a dipeptidyl-peptidase, whereas the N-terminal fragments are further broken down one amino acid at a time. In addition, [Dopa(5)][His(7)]-corazonin was detected. Upon synthesis, this unexpected molecular modification turned out to be biologically active in bringing about cuticular melanization. (c) 2005 Elsevier Inc. All rights reserved.