Collagen degradation is important in the pathogenesis of abdominal aortic aneurysms (AAA) but the enzymes responsible are undefined. Collagenase-3 is a recently described matrix metalloproteinase (MMP-13) with limited tissue distribution and a highly regulated pattern of expression. Using reverse transcription-polymerase chain reaction and Southern blots, amplification products corresponding to MMP-13 were uniformly detected in samples of AAA and atherosclerotic aorta (ATH), but not in normal aortic controls. By densitometric analysis of blots normalized to β-actin, the expression of MMP-13 was 1.8-fold higher in AAA compared to ATH (P < 0.05). Immunoreactive MMP-13 was localized to medial smooth muscle cells (SMC) in AAA tissue and to human vascular SMC in culture, which also expressed MMP-13 mRNA. These findings indicate for the first time that SMC production of MMP-13 may contribute to the pathophysiologic progression of AAA.