Background and preliminary data Cystic lung destruction is the hallmark of pulmonary LAM and generally results in respiratory failure over a variable period of time(Johnson 2006). Over-activity of proteases including elastase, trypsin and the matrix metalloproteinases (MMPs) is responsible for parenchymal destruction in emphysema and other lung diseases. The MMPs are a family of zinc dependent proteolytic enzymes with proteolytic activities against extra-cellular matrix proteins. The MMPs are overexpressed in inflammatory and neoplastic diseases where in addition to processing extra-cellular matrix they also have roles in metastasis, angiogenesis, growth factor activation and inactivation(Stamenkovic 2003). MMPs -1, -2, and -9 are involved in the sequential digestion of collagen and gelatin and are strongly expressed in the walls of cysts where it is thought they contribute to parenchymal destruction in LAM(Matsui, Takeda et al. 2000). Further, MMPs can be detected by gelatin zymography in the urine of patients with LAM but not controls. Doxycycline is a tetracycline antibiotic in common clinical use. In addition to its antimicrobial action it inhibits the synthesis and activity of several MMPs and inhibits proliferation of a range of cell types including arterial smooth muscle, cancer cells and cancer model systems(Bendeck, Conte et al. 2002; Duivenvoorden, Popovic et al. 2002; Onoda, Ono et al. 2004). In preliminary experiments we have demonstrated that primary LAM derived and angiomyolipoma cells produce MMP-2 and -7 and that MMP expression and proliferation in these cells in inhibited by doxycycline.