We have designed, developed, and assessed a novel preclinical positron emission tomography (PET) imaging system named ModPET. The system was developed using modular gamma cameras, originally developed for SPECT applications at the Center for Gamma Ray Imaging (CGRI), but configured for PET imaging by enabling coincidence timing. A pair of cameras are mounted on a exible system gantry that also allows for acquisition of optical images such that PET images can be registered to an anatomical reference. Data is acquired in a super list-mode form where raw PMT signals and event times are accumulated in events lists for each camera. Event parameter estimation of position and energy is carried out with maximum likelihood methods using careful camera calibrations accomplished with collimated beams of 511-keV photons and a new iterative mean-detector-response-function processing routine. Intrinsic lateral spatial resolution for 511-keV photons was found to be approximately 1.6 mm in each direction. Lists of coincidence pairs are found by comparing event times in the two independent camera lists. A timing window of 30 nanoseconds is used. By bringing the 4.5 inch square cameras in close proximity, with a 32-mm separation for mouse imaging, a solid angle coverage of ∼75% partially compensates for the relatively low stopping power in the 5-mm-thick NaI crystals to give a mea- sured sensitivity of up to 0.7%. An NECR analysis yields 11,000 pairs per second with 84 μCi of activity. A list-mode MLEM reconstruction algorithm was developed to reconstruct objects in a 88 x 88 x 30 mm field of view. Tomographic resolution tests with a phantom suggest a lateral resolution of 1.5 mm and a slightly degraded resolution of 2.5 mm in the direction normal to the camera faces. The system can also be configured to provide (99m)Tc planar scintigraphy images. Selected biological studies of inammation, apoptosis, tumor metabolism, and bone osteogenic activity are presented.