Relations between the structure of Fe-ZSM-5 catalysts prepared by interaction of FeCl3 with H-ZSM-5 and their catalytic behavior in the SCR of NO by isobutane were investigated by combining results of catalytic studies (1000 ppm NO, 1000 ppm isobutane, and 2% O-2 in He, 30,000 h(-1)) and of physicochemical characterization (XRD, EXAFS, Mossbauer spectroscopy, TPR, IR, XPS). By variation of the preparation conditions (method of FeCl3 introduction-chemical vapor deposition or solid-state ion exchange, washing intensity, calcination regime) and of the matrix (H-ZSM-5 with normal and high defect density), Fe-ZSM-5 materials with strongly varying properties (aggregation degree of the Fe phase, acidity) were obtained. Significant discrepancies between conclusions derived from EXAFS, TPR, and Mossbauer spectroscopy were ascribed to a preference of Mossbauer spectroscopy for the detection of aggregated phases and a high defectivity of Fe oxide clusters formed upon calcination. The critical step for the preparation of a highly disperse Fe phase is extensive washing after Fe introduction. The catalytic behavior of overexchanged Fe-ZSM-5 materials prepared by interaction of FeCl3 with H-ZSM-5 of normal defect density was not influenced by aggregation of a significant part of the Fe phase. The comparison of their catalytic properties with those of a Fe2O3/H-ZSM-5 mechanical mixture and of catalysts prepared by aqueous ion exchange or by CVD of FeCl3 into H-ZSM-5 of high defect density implies that the particular activity of overexchanged Fe-ZSM-5 arises from minority sites. In these, the Fe ions are probably isolated. Other Fe sites of low nuclearity appear to add to the activity. The poor SCR performance (at a given ability for isobutane activation) of Fe-ZSM-5 prepared with a defective ZSM-5 matrix may indicate that the Fe sites which provide the particular activity of overexchanged Fe-ZSM-5 require the cooperation of acidic sites.