We are pursuing the development of small-animal SPECT systems for imaging at low energies (such as iodine-125 emissions) based on silicon double-sided strip detectors together with multiple-pinhole apertures. We have conducted imaging studies of phantoms using a prototype system that utilizes a detector of 300-micrometer thickness and 50-micrometer strip pitch. Good spatial resolution can be achieved with a 23-pinhole aperture at low magnification (∼26 mm ROR, ∼7 mm aperture-detector separation). A next-generation system is currently under development that will use silicon detectors of greater thickness (1 mm) and active area (∼6 cm × 6 cm) deployed in a stacked configuration such that projection data will be acquired at multiple magnifications simultaneously. We expect this system to offer sub-millimeter spatial resolution in combination with good sensitivity.