Background. Improvement in the morphological appearance of collagen and elastic fibres has been reported after the use of trichloroacetic acid, dermabrasion and laser therapy, but the histopathological changes occurring after photodynamic therapy are less understood. Aim. To assess the histological changes that occur after methyl aminolevulinate (MAL) plus red-light therapy for facial photodamage. Methods. This was a prospective, double-blind, double-arm, randomized, placebo-controlled trial of MAL plus red light in patients with facial photodamage. A 3-mm punch biopsy was taken from each side of the face before randomization and start of therapy. A dermatopathologist blinded to the treatment assessed epidermal and dermal layer thickness, perivascular inflammation, solar elastosis, perifollicular fibrosis, telangiectasias, number of elastic and collagen fibres, and grade of reticular degeneration. Results. In total, 65 women were initially screened for eligibility, but skin samples from only 38 of these were analysed. The change in dermal thickness from baseline to postintervention was significant (P < 0.01, Wilcoxon signed rank test). Although there was a trend for the epidermis to be thinner after MAL plus red light vs. placebo plus red light (46.25 μm vs. 55.50 μm, respectively), the difference was not significant (P = 0.64, Mann–Whitney U-test). Similarly, the changes in dermal thickness obtained with the two treatments were not significant (P = 0.99, Mann–Whitney test). Histological improvement was seen using stains for collagen, elastic tissue, and perifollicular fibrosis after MAL plus red light therapy. Discussion. Dermal thickness increased after the use of MAL plus red light, and there was improvement in collagen, elastic tissue and perifollicular fibrosis. Although these differences were not significant, most of the histopathological features examined in our study improved after treatment with MAL plus red light. The lack of significance might be due either to the low power of this study or to the failure of our scoring method to detect significant histopathological differences.