The reaction pathways for thermal and photochemical formation of cyclobutane pyrimidine dimers in DNA are explored using density functional theory techniques. Although it is found that the thermal [2 2] cycloadditions of thymine thymine (T T → T⋄T), cytosine cytosine (C C → C⋄C) and cytosine thymine (C T → C⋄T) all are similarly unfavorable in terms of energy barriers and reaction energies, the excited-state energy curves associated with the corresponding photochemical cycloadditions display differences that—in line with experimental findings—unanimously point to the predominance of T⋄T in UV-irradiated DNA. It is shown that the photocycloaddition of thymines is facilitated by the fact that the S₁ state of the corresponding reactant complex lies comparatively high in energy. Moreover, at a nuclear configuration coinciding with the ground-state transition structure, the excited-state energy curve displays an absolute minimum only for the T T system. Finally, the T T system is also associated with the most favorable excited-state energy barriers and has the smallest S₂–S₀ energy gap at the ground-state transition structure.