A relative humidity‐moderated differential mobility optical particle size spectrometer (RH‐DMOPSS) was developed to measure particle size distributions at different humidity conditions in the 0.1‐ to 1.1‐μm size range. The system has a high‐flow differential mobility analyzer followed by an optical counter and condensation particle counter in parallel. An aerosol dryer or humidity conditioner can be placed in line ahead of the mobility analyzer. A second dryer ahead of the optical counter permits measurements of the decrease in particle size when particles classified at high relative humidity were dried. The RH‐DMOPSS data set includes (1) optical counter response to monodisperse ambient aerosols, (2) accumulation mode particle size distributions for dry and humid conditions, (3) selected hygroscopic growth factors for humid diameters of 0.2 to 1.1 μm, (4) inferred volatile particle water volume, and (5) inferred refractive index for dried particles. The RH‐DMOPSS was operated in Smoky Mountains National Park as part of the Southeastern Aerosol and Visibility Study and compared with other collocated size and aerosol growth measurements. For dried ambient particles, size distribution parameters were correlated with those from impactor measurements, but volume median diameters were 12% smaller, on average. Growth factors for particles below 0.5‐μm diameter were in the same range as those measured by a tandem differential mobility analyzer and, for all sizes, were consistent with the measured differences between dried and humidified particle size distributions. The mean ambient particle real refractive index inferred from the RH‐DMOPSS dry‐particle calibration data was 1.48, equal to that measured by a multiangle light‐scattering instrument.