OBJECTIVES: An in vivo rabbit model was used to study the effect of 3 hours of experimentally induced phonation on messenger RNA expression of the normal vocal fold. STUDY DESIGN: Prospective; animal model. SUBJECTS AND METHODS: Ten rabbits received experimental phonation for 3 hours, followed by 1 hour of recovery. A separate group of 5 rabbits served as no-phonation controls. We measured messenger RNA expression of matrix metalloproteinase-1, MMP-9, and interleukin-1beta using real-time reverse-transcribed polymerase chain reaction. Gene expression ratios from phonation and control animals were assessed with the Mann-Whitney U test. RESULTS: Phonation (77 +/- 3 dB; 429 +/- 141 Hz) resulted in increased matrix metalloproteinase-1 gene expression from rabbits receiving experimental phonation compared with controls, and a nonsignificant increase in matrix metalloproteinase-9 and interleukin-1beta gene expression. CONCLUSION: Matrix metalloproteinases play a role in maintaining tissue homeostasis. Investigation of cellular responses to experimental phonation may provide insight into how matrix metalloproteinases and other extracellular matrices contribute to maintenance of the vocal fold and development of pathology.