Density functional theory computations and nanosecond time-resolved resonance Raman (ns-TR3) spectroscopy experiments were done to study the photocyclization of 2-pyridyl pheryl ketone in acid solution. The most probable cyclization pathway was assigned to the reaction RX1, which had the lowest free-energy barrier. The factors that determine the free-energy barriers among the different reactions examined were discussed. Solvent effects on these reactions were also explored by calculations that included a polarizable continuum model for the bulk solvent effect.