Background. To optimize photodynamic therapy (PDT) and photodetection of cancer, two important variables that must be considered are the uptake of the dye and the dye contrast between normal and neoplastic tissue after injection. Methods. To study these variables in a clinical context, an apparatus based on a noninvasive optical fiber that detects the dye by light- induced fluorescence (LIF) was constructed. Results. Studies on the pharmacokinetics of the fluorescent fraction of Photofrin in patients with early squamous cell carcinoma in the oral cavity, esophagus or bronchi show a signal contrast ranging from 1.5 to 3.5 a short time after intravenous injection that rapidly decreases and tends to unity (one) about 12 hours later. The magnitude of this contrast appears to correlate with the staging of the cancer, the more invasive tumors showing the highest contrast. The more invasive tumors also show the highest uptake. The oral cavity pharmacokinetics are similar to those found in the esophagus and the bronchi. Conclusions. The oral cavity appears to be a good model, with easy access for optimizing photodetection and PDT in the esophagus and the bronchi. These pharmacokinetics can be used directly for optimizing photodetection. However, complementary information on the detailed localization of the drug by fluorescence microscopy and a correlation of these data with tumor necrosis efficacy are necessary to optimize PDT timing and therapeutic gain.