The objective of the present study was to determine the effects of hydroxypropyl-beta-cyclodextrin (HPCD) complexation on the transdermal penetration and photostability of a model ultraviolet A (UVA) absorber, butyl methoxydibenzoylmethane (avobenzone), and to determine the influence of complexation on in vivo photoprotection. Avobenzone-HPCD complexation was demonstrated by differential scanning calorimetry. Formulations containing 0.12 mg/ml avobenzone and up to 30% (w/w) HPCD were prepared. Transdermal penetration was conducted using a modified Franz diffusion cell apparatus. As the concentration of HPCD was increased from 0% to 20%, transdermal permeation increased. Maximum flux occurred at 20% HPCD, where sufficient cyclodextrin was present to completely solubilize all avobenzone. When the concentration of HPCD was increased to 30%, transdermal penetration decreased, suggesting the formation of an avobenzone reservoir on the skin surface. Photostability of avobenzone was investigated under 100, 250, and 500 kJ/m2 UVA irradiation. The 30% HPCD formulation was the most photostable, followed by 20%, 10%, and 0% formulations. In vivo, the 30% HPCD formulation afforded the best photoprotection, as evidenced by the lowest extent of sunburn cell formation and edema induction. This work indicates that inclusion of HPCD in sunscreen formulations may enhance photoprotection by reducing both skin penetration and photodecomposition of UV absorbers.