We present the results of a series of spectroscopic measurements made in vivo in patients undergoing photodynamic therapy (PDT). The patients studied here were enrolled in Phase II clinical trials of Photofrin-mediated PDT for the treatment of non-small cell lung cancer and cancers with pleural effusion. Patients were given Photofrin at dose of 2 mg per kg body weight 24 hours prior to treatment. Each patient received surgical debulking of the tumor followed by intracavity PDT at 630nm to a dose of 60 J/cm2. Dose was monitored continuously using implanted isotropic fiber-based light detectors. We measured the diffuse reflectance spectra before and after PDT in various positions within the cavity, including tumor, diaphragm, pericardium, skin, and chest wall muscle in 10 patients. The measurements were acquired using a specially designed fiber optic-based probe consisting of one fluorescence excitation fiber, one white light delivery fiber, and 9 detection fibers spaced at distances from 0.36 to 7.8 mm from the source, all of which are imaged via a spectrograph onto a CCD, allowing measurement of radially-resolved diffuse reflectance and fluorescence spectra. The absorption spectra were analyzed using an analytical model of light propagation in diffuse media based on the P3 approximation to radiative transport, assuming a known basis set of absorbers including hemoglobin in its oxygenated and deoxygenated forms and Photofrin. We find significant variation in hemodynamics and sensitizer concentration among patients and within tissues in a single patient.