Various chronic disease processes are characterized by progressive accumulation of connective tissue under-going fibrotic degeneration. Evidence of oxidative reactions is often associated with fibrogenesis occurring in liver, lung, arteries, and nervous system. Moreover, an increasing bulk of experimental and clinical data supports a contributory role of oxidative stress in the pathogenesis of this kind of disease. Indeed, many etiological agents of fibrogenesis stimulate free radical reactions either directly or through inflammatory stimuli. Free radicals, as well as products of their reaction with biomolecules, appear to modulate the activity of the two cellular types mainly involved in the process, namely phagocytes and extracellular matrix-producing cells. Lipid peroxidation and certain lipid peroxidation products induce genetic overexpression of fibrogenic cytokines, the key molecules in the pathomechanisms of fibrosis, as well as increased transcription and synthesis of collagen. Both these events can be downregulated, at least in experimental models, by the use of antioxidants. The effect of oxidative stress on cytokine gene expression appears to be an important mechanism by which it promotes connective tissue deposition.