We have studied the fate of two chemicals related to poison ivy catechols after their administration to guinea pigs by the topical and oral routes. Tritiated pentadecylcatechol (PDC), a sensitizer and a tolerogen, and tritiated pentadecylveratrole (PDV), a nonsensitizer and nontolerogen, were rapidly absorbed into the serum after administration by either route and were also found in tissues in excess of their serum content. Although serum levels of PDC were higher than those of PDV after topical administration, the reverse was true after the oral route. Excretion of both chemicals was mainly via the feces but some was also found in urine. Because of the persistence of PDC (and to a lesser extent of PDV) in the bile (but not the serum and urine) an enterohepatic circulation of these materials was felt to exist and to be related to the induction of tolerance. After topical administration of PDC a biphasic pattern of radioactive uptake was found in the draining but not the opposite inguinal lymph nodes. Radioactivity rapidly declined in the draining nodes after the onset of sensitivity. The draining lymph nodes of PDV-treated animals showed a saturation-like uptake of radioactivity with only slight decline over the month after administration. There was no difference between draining mesenteric and nondraining inguinal nodes after oral PDC or PDV; after oral PDC, however, a rapid uptake and loss of radioactivity occurred which was not due to serum entrapment by the nodes. This data suggests that the induction of tolerance is associated with the entry of free PDC or its metabolites into the lymph nodes via the blood stream whereas sensitization is associated with entry via the lymphatics. PDC was rapidly cleared from the site of application after the onset of sensitivity; the rate of PDV skin clearance was constant. It is possible that delayed contact sensitivity is associated with a phenomenon similar to the immune clearance of soluble antigens.