Fouling is a major problem that limits the wider application of membranes for liquid separations. Progress towards improved methods for the control of this generally complex process would be facilitated by the development of additional techniques for the study of fouling under realistic operating conditions. This paper describes a novel approach to the real-time, noninvasive, in situ measurement of membrane fouling using ultrasonic time-domain reflectometry (TDR). Membrane fouling of commercial composite membranes was studied during reverse osmosis desalination of calcium sulfate solutions at three different axial velocities under conditions of constant feed pressure and concentration. The ultrasonic TDR measurements are compared with traditional indicators of fouling including flux decline, changes in permeate concentration, and magnitude of membrane surface coverage. Overall, the results show a good correspondence between the decline in the ultrasonic signal amplitude and the development of a fouling layer. In addition, the data suggest that ultrasonic TDR may be particularly responsive to fouling layer initiation and its subsequent removal during membrane cleaning. While the present results show promise, additional work is required to fully evaluate the capabilities of the technique and its applicability in commercial membrane separation systems.