Groundwater discharge to the Cockburn River, southeast Australia, has been estimated from comparison of natural 222Rn activities in groundwater and river water, interpreted using a numerical flow model that simulates longitudinal radon activities as a function of groundwater inflow, hyporheic exchange, evaporation, gas exchange with the atmosphere, and radioactive decay. An injection of SF6 into the river to estimate the gas transfer velocity assisted in constraining the model. Previous estimates of groundwater inflow using 222Rn activities have not considered possible input of radon due to exchange between river water and water in the hyporheic zone beneath the streambed. In this paper, radon input due to hyporheic exchange is estimated from measurements of radon production by hyporheic zone sediments and rates of water exchange between the river and the hyporheic zone. Total groundwater inflow to the Cockburn River is estimated to be 18500 m3/d, although failure to consider hyporheic exchange would cause overestimation of the volume of groundwater inflow by approximately 70%.