Site-isolated [Ir-4(CO)(12)] on the surface of TiO2 powder (calcined at 200 or 400 degreesC) was prepared by deposition of [Ir-4(CO)(12)] from n-hexane solution and, alternatively, by reductive carbonylation of TiO2-supported [Ir(CO)(2)(acac)] in the presence of CO at 1 atm and 100 degreesC. The preparation of the supported clusters and their subsequent decarbonylation by treatment in He or H, were characterized by infrared (IR) and extended X-ray absorption fine structure (EXAFS) spectroscopies. The first-shell Ir-Ir coordination number representing the supported iridium carbonyl clusters was found to be 3.0 +/- 0.3, with an Ir-Ir bond distance of 2.68 +/- 0.03 Angstrom, consistent with X-ray diffraction data characterizing crystalline [Ir-4(CO)(12)]. Decarbonylation in He at 300 degreesC gave TiO2-supported clusters retaining the tetrahedral Ir-4 frame of the precursor [Ir-4(CO)(12)], with an Ir-Ir first-shell coordination number of 3.0 +/- 0.3. In contrast, decarbonylation of TiO2-supported [Ir-4(CO)(12)] in H, at 300 degreesC led to (nonuniform) aggregated iridium clusters with an Ir-Ir first-shell coordination number of 5.0 +/- 1.0, a second-shell Ir-Ir coordination number of 2.0 +/- 0.5. and a third-shell Ir-Ir coordination number of 7.0 +/- 1.0. The chemistry on the TiO2 surface is consistent with the known solution and surface chemistry of iridium carbonyls. The site-isolated tetrairidium clusters on TiO2 are among the simplest and best-defined supported metals.