Detectable contact hypersensitivity in mice after conventional sensitization procedures is relatively shortlived, in contrast to the long-lived reactivity that follows sensitization in man and quinea pigs. Furthermore, deliberate oral feeding of reactive haptens to mice before epicutaneous sensitization has been shown to suppress their ability to express reactivity when subsequently challenged. We have observed augmented contact hypersensitivity responses in BALB/c mice in whom oral grooming of the abdominal skin site of sensitization with DNFB is prevented by a variety of procedures, including wrapping a plaster cast around the thorax. The augmented responses in casted mice were observed after topical sensitization with amounts of DNFB ranging from suboptimal to supraoptimal; casted mice were able to express contact hypersensitivity reactivity after sensitization with considerable smaller amounts of hapten than conventionally sensitized animals. Delaying application of the cast for 6 hr after sensitization abrogated the enhancing effect seen with immediate casting. The enhancing effect of casting on contact hypersensitivity reactions was not observed for other delayed-in-time reactions in which casted animals were immunized via nonepicutaneous routes - i.e., no enhancement was seen of delayed reactions elicited after i.v. immunization with sheep erythrocytes or subcutaneous immunization with haptenated lymphoid cells. Finally, the duration of detectable hypersensitivity after sensitization with suboptimal amounts of DNFB significantly prolonged to at least 29 days if mice were casted immediately after skin painting. These results are consistent with the hypothesis that at least some aspects of down-regulation of contact hypersensitivity in mice after conventional sensitization procedures are activated by oral ingestion of free and/or conjugated hapten that occurs secondary to the vigorous oral grooming of the skin-painted site. By eliminating this route of hapten administration, not only can lower doses of hapten be used for sensitization, but both the magnitude and the duration of detectable hypersensitivity can be enhanced.