A hydrophilic matrix tablet containing 300 mg of propylthiouracil was formulated with several types of hydroxypropylmethylcellulose. The influence of polymer and drug granule particle size, polymer concentration, crystallinity and geometry of the polymer particles, the polymer incorporation outside or inside the granule, addition of a filler and tablet hardness were studied. Polymer concentration, polymer particle size and geometry, filler addition and type of the filler used had a major influence on in vitro drug dissolution profiles. The bioavailability of propylthiouracil in dogs from the hydrophilic matrices investigated was low, because of the short gastro-intestinal transit times of the matrix tablets in the dogs. The matrix tablets reached the colon in fasted dogs within 2-3 hours after administration. The results indicated the poor predictability of bioavailability experiments in dogs with hydrophilic matrices. Although the bioavailability data in pigs seemed promising, a transit time study revealed a long stomach residence time of the matrix tablets in pigs. These data suggested that pigs are an inappropriate animal model for bioavailability studies of erodible matrix tablets.