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The objective of this study was to develop a light delivery and measurement device for photodynamic therapy (PDT) in the nasopharyngeal cavity, which achieves a homogeneous and reproducible fluence rate distribution to a target area and provides proper shielding of predefined risk areas. Materials and Methods A flexible silicone applicator was developed, incorporating light delivery and dosimetry fibers. The applicator can be inserted through the mouth and fixed in the nasopharyngeal cavity. Tissue optical phantoms were prepared on the basis of optical properties measured in vivo using diffuse reflectance spectroscopy (DRS). The fluence rate over the length of the applicator surface was measured in air, in tissue optical phantoms and in five healthy volunteers. Results The fluence rate distribution over the applicator surface in air and tissue optical phantom was found to be more homogeneous (SD/mean 3.8% and 18.3%, respectively) than the fluence rate distribution in five volunteers (SD/mean ranging from 19% up to 52%). The maximum observed fluence rate build-up in the nasopharynx varied between subjects and ranged from a factor of 4.1–6.9. Shielding of the risk area such as the soft palate and tongue was effective. Conclusions In air and in tissue optical phantoms the fluence rate distribution of the device was highly homogeneous. The observed inter-subject and intra-subject variations in fluence rate in healthy volunteers originated from differences in optical properties and nasopharyngeal geometry. Light delivery based on a single tissue surface measurement will not be adequate. In situ dosimetric measurements are required to determine the light fluence delivered to a geometrically complex site such as the nasopharynx. These observations should be taken in consideration when developing light applicators for PDT of the nasopharynx and other non-uniform surfaces. Lasers Surg. Med. 39:647–653, 2007. © 2007 Wiley-Liss, Inc.