Femtosecond time-resolved infrared spectroscopy was used to study the formation of cyclobutane dimers in the all-thymine oligodeoxynucleotide (dT)₁₈ by ultraviolet light at 272 nanometers. The appearance of marker bands in the time-resolved spectra indicates that the dimers are fully formed ∼1 picosecond after ultraviolet excitation. The ultrafast appearance of this mutagenic photolesion points to an excited-state reaction that is approximately barrierless for bases that are properly oriented at the instant of light absorption. The low quantum yield of this photoreaction is proposed to result from infrequent conformational states in the unexcited polymer, revealing a strong link between conformation before light absorption and photodamage.