Fundamental to both is the absorption of photons of light by a chromophore. However, once this event occurs, the mechanisms leading to cellular damage diverge.

In phototoxic reactions the photosensitivity is mediated by non-immunologic mechanisms. Absorption of photons of a specific wavelength (UVA in nearly all cases) by the photosensitizing chromophore results in electrons changing their orbits and creating unstable singlet or triplet states, which release
energy when the molecule returns to a stable ground state. This energy causes cellular damage and the release of products of inflammation, as well as free radicals, causing cellular damage and resultant erythema, edema, and occasionally vesiculation, i.e., an exaggerated sunburn reaction, which is restricted to sun-exposed areas. This reaction can occur upon first exposure to the drug.These chromophores are typically polycyclic ring structures withalternating single and double bonds, and fluorination at critical sites onthe molecule. The fluoroquinolones are typical examples, as are the porphyrins. Apart from sunburn, phototoxic drug eruptions are the commonest photosensitivity reactions.

In photoallergic reactions, following absorption of the specific photons, a new compound is formed, which acts as a haptene. This molecule then combines with a protein to form a complete antigen, which possesses immunologic properties. The mechanism of the host response is then similar to other forms
of delayed hypersensitivity and is mediated by T-lymphocytes. Morphologically, this response presents as an eczematous eruption, and while it may start in sun exposed areas, it may spread to non-sun exposed parts of the body. These reactions are relatively unusual and require at least one prior exposure to the drug
Diseases such as discoid and systemic lupus, PMLE, solar urticaria, and dermatomyositis may also fall into this category, although their morphologies vary widely.