The thermal and photochemistry of tert-butyl iodide (t-buI) dosed at 100 K on rutile TiO2(110) has been studied using isothermal and temperature programmed desorption mass spectrometry. Nondissociative adsorption and desorption dominate the thermal behavior with dose-dependent t-buI desorption peaks at nominally 220 and 150 K. Ultraviolet photochemistry occurs readily, but the behavior of submonolayers and multilayers differ qualitatively. Ejection of t-buI and i-C4H8 dominate during submonolayer photolysis at 100 K. Multilayer photolysis results are also dominated by ejection during irradiation, but the t-buI component is strongly suppressed, and the maximum rates of i-C4H8 and HI ejection did not occur at the outset. A mechanistic model capturing the observations involves both direct and substrate-mediated electronic excitation of t-buI. According to this model, ejection of t-bu(I) occurs only from transient substrate-mediated formation of anionic t-buI. For either excitation path, the C-I dissociation probability is significant, and the excited tert-butyl product rear-ranges readily to form i-C4H8 that is ejected. For any local region where there is multilayer coverage, products formed at the adsorbate-vacuum interface are ejected promptly, but products formed within the multilayer are trapped. Thus, ejection of t-buI is suppressed, and trapped primary photodissociation products, tert-butyl and 1, react to either reform t-buI or rearrange to i-C4H8 and HI. The latter two products remain trapped and are subsequently induced to desorb by acquisition of momentum from collisions with subsequently formed translationally excited photodissociation products.