A single painting or daily paintings for 5 days with dinitrofluorobenzene (DNFB) on the abdominal skin of mice induced both contact sensitivity, detectable by ear swelling, and, hapten-reactive helper T cells, detectable by the augmented anti-bovine serum albumin (BSA) antibody response on challenge with dinitrophenyl-BSA. Contact sensitivity was induced within 7 days and helper activity within 14 days after the sensitization. Anti-hapten antibody response in the spleen or regional lymph nodes of such mice, however, was negligibly small during the 15 days after a single painting. Failure to respond with anti-hapten antibody production of mice given only a single painting was shown to be due to the shortage of B cells reactive to the hapten. Daily paintings for 5 days did not necessarily result in the augmented antibody response. By contrast, a strong anti-hapten antibody response was observed in mice receiving two paintings at an interval of 10 days. In these mice, hapten-specific B memory cells as well as hapten-reactive T cells were detected. Thus, the anti-hapten antibody response after the topical applciation of simple chemicals may depend upon the priming of B cells, and the response must be mediated by the cooperation of T and B cells both reactive to the antigen.