2,4,6-Trinitrochlorobenzene (picryl chloride) and 2,4-dinitrochlorobenzene (DNCB) fail to cross-sensitize with respect to contact sensitivity in mice. Nevertheless, topical exposure of mice to DNCB and other skin-sensitizing dinitrobenzene derivatives was found to result in a significant impairment of draining lymph node cell proliferative responses induced following epicutaneous challenge with picryl chloride 5 days later. The inhibition of picryl chloride induced proliferation was associated with an impairment of contact sensitization to this chemical. The effect of DNCB on subsequent responses to picryl chloride was transient and no longer detectable 15 days following exposure. The inhibition of proliferation and contact sensitization caused by DNCB was largely restricted to picryl chloride. Thus, DNCB failed to influence the development of contact allergy to the unrelated chemical 4-ethoxymethylene-2-phenyloxazol-5-one (oxazolone) and exerted a far less pronounced effect on oxazolone-induced proliferative responses. These data, therefore, describe an antigen-restricted form of antigenic competition which is associated with a depression of the primary lymphocyte proliferative response.