Whole-genome microarray analysis of Geobacter sulfurreducens grown on insoluble Fe(III) oxide or Mn(IV) oxide versus soluble Fe(III) citrate revealed significantly different expression patterns. The most upregulated genes, omcS and omcT, encode cell-surface c-type cytochromes, OmcS being required for Fe(III) and Mn(IV) oxide reduction. Other electron transport genes upregulated on both metal oxides included genes encoding putative menaquinol : ferricytochrome c oxidoreductase complexes Cbc4 and Cbc5, periplasmic c-type cytochromes Dhc2 and PccF, outer membrane c-type cytochromes OmcC, OmcG and OmcV, multicopper oxidase OmpB, the structural components of electrically conductive pili, PilA-N and PilA-C, and enzymes that detoxify reactive oxygen/nitrogen species. Genes upregulated on Fe(III) oxide encode putative menaquinol : ferricytochrome c oxidoreductase complexes Cbc3 and Cbc6, periplasmic c-type cytochromes, including PccG and PccJ, and outer membrane c-type cytochromes, including OmcA, OmcE, OmcH, OmcL, OmcN, OmcO and OmcP. Electron transport genes upregulated on Mn(IV) oxide encode periplasmic c-type cytochromes PccR, PgcA, PpcA and PpcD, outer membrane c-type cytochromes OmaB/OmaC, OmcB and OmcZ, multicopper oxidase OmpC and menaquinone-reducing enzymes. Genetic studies indicated that MacA, OmcB, OmcF, OmcG, OmcH, OmcI, OmcJ, OmcM, OmcV and PccH, the putative Cbc5 complex subunit CbcC and the putative Cbc3 complex subunit CbcV are important for reduction of Fe(III) oxide but not essential for Mn(IV) oxide reduction. Gene expression patterns for Geobacter uraniireducens were similar. These results demonstrate that the physiology of Fe(III)-reducing bacteria differs significantly during growth on different insoluble and soluble electron acceptors and emphasize the importance of c-type cytochromes for extracellular electron transfer in G. sulfurreducens.