Medical imaging using single gamma-ray-emitting radionuclides typically makes use of parallel hole collimators or pinholes in order to achieve good spatial resolution. However, a tradeoff in sensitivity is inherent in the use of a collimator, and modern preclinical single photon emission computed tomography (SPECT) systems detect a very small fraction of emitted gamma rays, often less than 0.1%. A system for small animal SPECT imaging which uses no collimators could potentially achieve very high sensitivity-several tens of percent-with reasonably sized detectors. This would allow two significant improvements in preclinical studies: images could be obtained more rapidly, allowing higher throughput for screening applications, or for dynamic processes to be observed with very good time resolution; and images could be obtained with less radioactive tracer, making possible the in vivo imaging of low-capacity receptor systems, aiding research into new tracer compounds, and reducing the cost and easing the regulatory burden of an experiment. Of course, a system with no collimator will not be able to approach the submillimeter spatial resolutions produced by the most advanced pinhole and collimated systems, but a high-sensitivity system with resolution of order 1 cm could nonetheless find significant and new use in the many molecular imaging applications which do not require good spatial resolution-for example, screening applications for drug development or new imaging agents. Rather than as an alternative to high-resolution SPECT systems, the high-sensitivity system is proposed as a radiotracer alternative to optical imaging for small animals. We have developed a prototype system for mouse imaging applications. The scanner consists of two large, thin, closely spaced scintillation detectors. Simulation studies indicate that a FWHM spatial resolution of 7 mm is possible. In an in vivo mouse imaging study using the (99m)Tc labeled tracer MAG-3, the sensitivity of the system is measured to be 40%. Simple projection images created by analytically combining the two detectors' data show sufficient resolution to observe the dynamic distribution of the radiotracer in the mouse.