alpha-Santonin 1 is a naturally occurring sesquiterpene lactone of significant historical interest. Not only is its solid-state photochemistry the oldest documented for an organic compound, but it is also the first drug to have been formulated in the United States. Not surprisingly, while its photochemical behavior in solution has been relatively well-established, its solid-state photoreactivity has not been thoroughly characterized. In this communication, with a combination of polarizing microscopy, single-crystal X-ray diffraction, spectroscopic methods, chemical trapping, and product analyses, we have confirmed a remarkable sequence of events that includes three consecutive solid-state reactions. The first step is a remarkably phase-selective and site-specific single-crystal-to-single photorearrangement of 1 into the previously postulated cyclopentadienone intermediate 2. The second step is a highly stereoselective Diels-Alder reaction to form a transient topochemical dimer, and the third step is an intramolecular 2 pi + 2 pi photodimerization to form the cage dimer 4 as the final product. Cyclopentadienone 2 was characterized in situ by single-crystal X-ray diffraction analysis as well as by electronic and vibrational spectroscopies. The intermediate cyclopentadienone 2 was also trapped as the [4 pi + 2 pi] cycloadduct 8 by an interfacial solid-liquid reaction between a photoreacted sample and dimethyl acetylene dicarboxylate (DMAD).