We describe a digital cross-correlation instrument that employs a radio-frequency mixer and a radionuclide-scintillation light source to measure fluorescence lifetimes. The digital approach provides single-photon sensitivity and accurate lifetime analysis even at low sample concentrations. The unique characteristics of the scintillation excitation source, coupled with the simplicity of mixer-based signal processing, give this approach particular appeal over traditional instrumentation used for excited-state decay measurements. We discuss the system design and evaluate its performance using two optical configurations. The close-packed configuration provides an indication of the general fluorescence detection limits which can be expected from measurements made with scintillation-based light sources. After applying a procedure to correct for systematic error caused by the mixer diode-bias potential, the results from the digital system demonstrate lifetime accuracy over a range of sample concentrations (nM–mM). Finally, we develop a modified detection sensitivity parameter and calculate its value to be1×10−3 s photon−1 pathlength−1for our experiments. This new parameter can assist in the design of other scintillation-based lifetime measuring devices. ©1998 American Institute of Physics.