Complex chromosome aberrations are characteristically induced after exposure to low doses of densely ionizing radiation, but little is understood about their formation. To address this issue, we irradiated human peripheral blood lymphocytes in vitro with 0.5 Gy densely ionizing alpha-particles (mean of 1 alpha-particle/cell) and analyzed the chromosome aberrations produced by using 24-color multiplex fluorescence in situ hybridization (M-FISH). Our data suggest that complex formation is a consequence of direct nuclear alpha-particle traversal and show that the likely product of illegitimate repair of damage from a single alpha-particle is a single complex exchange. From an assessment of the "cycle structure" of each complex exchange we predict alpha-particle-induced damage to be repaired at specific localized sites, and complexes to be formed as cumulative products of this repair.