BSA-Ph is a product of covalent coupling of p-aminophenytoin to bovine serum albumin (BSA). Hartley strain guinea pigs were immunized initially with BSA-Ph in Freund's complete adjuvant and 6 weeks later all animals received a booster injection of the same antigen as an emulsion in Freund's incomplete adjuvant; these injections were administered subcutaneously in the back of the neck and haunches. 4 weeks later, various antigens (BSA-Ph, BSA, EA-Ph and EA) which were dissolved in 0.1 ml of saline were injected in the foot pad of sensitized guinea pigs and the volume of the injected foot was measured at 48 hr after antigen injection. Remarkable swelling of the foot was induced in the animals challenged with BSA-Ph but not with the others. Macrophages obtained from the abdominal cavity of the sensitized animals were injected with various antigens in the skin of normal guinea pigs. At the injection sites, an area of erythema developed and this was followed by the development of indurated nodules over the next 24 to 48 hr. When Ph was given to guinea pigs through the mouth, fairly large amounts of Ph were detected in the gingiva and there was a good correlation between the tissue concentration of Ph and the serum Ph concentration. These findings strongly suggest that delayed-type allergy can be a possible reason for gingival hyperplasia after Ph administration.