The crystal structures of RCC1 and the Sec7 domain of human Arno, nucleotide exchange factors for the Ras-related GTPases Ran and ARF, reveal two very different folds, the former a seven-bladed β-propeller, the latter a capped right-handed superhelix. Both are also unrelated to the folds of Mss4 and elongation factor Ts, nucleotide exchange factors for Rab and elongation factor Tu.