This study was designed to preliminarily evaluate the use of positron emission tomography (PET) with [18F]-2-fluoro-2-deoxy-D-glucose (FDG) for monitoring chemotherapy effects, using a nude-mouse model of human nonsmall-cell lung cancer (NSCLC), the Lu-99 cell line. Tumor-FDG uptakes and volumes were measured after administrating a single dose of mitomycin (MMC) and vinblastine (VLB) and then compared these for a nontherapy group. A significant reduction in tumor volume after either chemotherapy occurred and associated with significantly lower FDG uptake values than the control group (p < 0.001), as early as day 1. These observations suggest that FDG-PET may be useful for noninvasively monitoring the effects of cancer chemotherapy.