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The primary symptoms of many vasculitides resemble those of infectious diseases. Patients with Wegener's granulomatosis usually seek medical care for respiratory tract symptoms resembling those caused by infection or allergy. In addition, vasculitis is a well-documented manifestation of infection by some known microbial agents. There have been relatively few controlled studies, however, seeking to identify infectious agents as the triggering factors in systemic vasculitides. Molecular methods offer powerful approaches for the identification of infectious agents in diseases of previously unknown origin. These methods include broad-range amplification of microbial nucleic acid sequences and comparative or subtractive methods, such as differential display and representational difference analysis. Host gene expression profiles (using DMA-chip technology) may also provide clues as to the possible infectious cause of an idiopathic disease. Furthermore, the application of molecular methods may reveal pathologic mechanisms and novel therapeutic strategies for the vasculitides.