An increasing body of evidence supports the usefulness of photodynamic therapy (PDT) in the treatment of non-neoplastic pathological conditions, including genital warts. In particular, PDT has demonstrated good clinical cure rates and low recurrence, and is now suggested as a safe alternative means of treating condylomata. To confirm the suitability of aminolaevulinic acid (ALA)-PDT for the treatment of this condition and to investigate the recruitment and significance of immune cells in lesional areas by immunohistochemical analysis at different time intervals after treatment. Fifteen subjects with histologically proven, recalcitrant condylomata acuminata of the penis, urethra, vulva or perianal area underwent several cycles of PDT following ALA application. Biopsies were taken at baseline and at different intervals during the trial, and infiltrating immune cells, CD3, CD4, CD8, CD1a and CD68, were evaluated by double immunocytochemical alkaline phosphatase antialkaline phosphatase (APAAP) staining. Our trial provided a complete cure rate of nine of 15 subjects after five PDT sessions. Perianal lesions showed a particularly rapid remission. While progressing towards total lesion clearance, the immunohistochemical pattern was dominated by dense CD4+ T lymphocytes infiltrating the superficial dermis, accompanied by an accumulation of Langerhans cells. Simultaneously, CD8 began to increase in the lesions of responding patients, and Langerhans cells seemed to migrate towards the dermis. CD68+ macrophages apparently did not participate in the immune inflammatory response. This study, to the best of our knowledge, represents the first attempt to clarify the effect of ALA-PDT on infiltrating immune cells in condylomata acuminata. Our results appear to confirm previously reported clinical data, suggesting that rapid activation of specific immunity in lesional skin, CD4+ T lymphocytes and dendritic cells could be responsible for healing. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.