To determine the importance of the regional lymph node in sensitization and tolerance, we applied five simple chemicals to alymphatic skin islands and to intact skin of guinea pigs. These chemicals were found to be divisible into two groups according to their sensitizing and toleragenic properties. Three compounds were sensitizers when injected in complete Freund's adjuvant and induced delayed contact sensitivity and immunologic tolerance when applied to skin islands or to intact skin. The other two compounds were also sensitizers when injected in complete Freund's adjuvant, but induced no sensitivity when applied to intact skin or to skin islands. This latter group of chemicals induced marked tolerance when applied to intact skin, and no tolerance when applied to alymphatic skin islands. Therefore, lymphatic connections between skin and regional lymph nodes were necessary for the development of tolerance to these simple chemicals but were not required for sensitization.

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