It is difficult to retain and localize radioactive, water-soluble compounds within plant cells. Existing techniques retain water-soluble compounds with varying rates of efficiency and are limited to processing only a few samples at one time. We developed a modified pressure infiltration technique for the preparation of microautoradiographs of 14C-labeled, water-soluble compounds in plant tissue. Samples from cottonwood (Populus deltoides Bartr. ex Marsh.) labeled with 14C were excised, quick frozen in liquid N2, freeze-dried at −50°C, and pressure-infiltrated with epoxy resin without intermediate solvents or prolonged incubation times. The technique facilitates the mass processing of samples for microautoradiography, gives good cellular retention of labeled water-soluble compounds, and is highly reproducible.