Contact hypersensitivity to dinitrochlorobenzene (DNCB), picryl chloride (PCI) or oxazolone was induced in mice by skin painting with these agents, and was measured by skin testing in vivo using the ear swelling method. Prior adminstration of dinitrobenzene sulfonate (DNBS) or picryl sulfonic acid prevented sensitization to DNCB and PCI, respectively. Both this tolerization and the original sensitization were specific for the hapten used. Cyclophosphamide given before sensitization enhanced skin reactions, but when given before tolerization it interfered with establishment of tolerance. Cells from both sensitized and tolerized mice were shown to be reactive with the corresponding haptens in vitro in the leukocyte adherence inhibition (LAI) reaction. LAI specificity was similar to that found for cutaneous reactivity. The reaction of DNCB-sensitized cells with DNBS led to the production of a soluble mediator which induced LAI in normal cells. The demonstration of potentially reactive cells in mice judged to be tolerant by skin testing indicates the concomitant existence of suppressor factors.