Migration of a water-soluble drug, propoxyphene hydrochloride, during drying of tablet granulations was studied. Wet granulations of the drug were prepared using lactose as the major diluent and corn starch as a disintegrant. Particle-size fractions of lactose ranging from 53 to 177 micron in diameter were employed in different granulations to examine the effect of particle size of the major diluent on drug migration. Determination of drug concentration at various depths in a dried granulation bed was accomplished by using a drying cell consisting of four layers. A numerical coefficient of migration was developed to compare the extent of drug migration in the various lactose granulations. Migration increased with decreasing particle size of the major diluent, lactose. Two factors that may contribute to increased migration with smaller particles are increased entry suction due to decreased intragranular capillary size and increased intergranular contact area.