BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) combines photosensitizers absorbing light in the visible spectral region and irradiation with light of corresponding wavelengths. We analysed the sensitivity of cell lines established from resident cutaneous cells and from transformed lymphocytes towards PDT. STUDY DESIGN/MATERIALS AND METHODS: PDT was performed employing either 630 or 662 nm light or polychromatic red light (600-700 nm) and photosensitizers Photosan-3, delta-aminolevulinic acid, or methylene blue. Proliferation measured by 3H-TdR uptake was determined in human immortalized keratinocytes (HaCaT) and mouse fibroblasts (NIH/3T3) in comparison to human transformed T-(HuT78) and B-lymphocytes (RA1). Additionally, uptake of the photosensitizers was estimated employing video-intensified fluorescence-microscopy (VIFM). RESULTS: Depending on the photosensitizer tested HaCaT and NIH/3T3 exhibited an ED50 up to 10-fold as high as the lymphocytic lines. Polychromatic red light was at least as effective at inducing photodynamic reactions as 630 or 662 nm light. VIFM revealed a positive correlation between sensitivity of a given cell type towards PDT and uptake of the photosensitizers. The differential uptake observed in vitro was confirmed in vivo: A photosensitizer applied topically on a lesion of a patient with mycosis fungoides was found to accumulate preferentially in the lymphocytic infiltrate. CONCLUSION: Selective topical polychromatic PDT seems to be a feasible goal for the treatment of cutaneous lymphomas.