Summary Thin-layer and paper chroma-tography have been used to study the metabolism of promazine following its oral administration to man and animals. Humans excrete about 33% of the drug in urine, in the form of 26-30 derivatives. These compounds are distributed between nonphenolic (14%) and phenolic (19%) fractions in the ratio of 1 to 1.4. The principal metabolites are nor2promazine sulfoxide (6.3%), nor1-promazine sulfoxide (5.2%), 3-hydroxy-promazine glucuronide (3.7%), 3-hydroxy-noripromazine glucuronide (3.1%), and the glucuronides of L4 and L5 (5.5%). In addition to the desmethyl sulfoxides, the non-phenolic fraction contains promazine-N-ox-ide, promazine sulfoxide, unchanged promazine, nor1promazine and traces of nor2proma-zine. The phenolic fractions consist of glucuronides (15%), ethereal sulfates (3%) and unconjugated phenols (1-2%). The compounds bound to glucuronic acid include 3-hydroxypromazine and its 2 desmethyl derivatives, the 3 corresponding sulfoxides, and L4 and L5. 3-Hydroxypromazine and 3-hydroxy-nor1promazine and their sulfoxides are also excreted as ethereal sulfates. Relatively small amounts of the drug are voided by dogs (13%) and rabbits (10-13%). Furthermore, these animals exhibit markedly different excretion patterns. The metabolites in dog urine are present for the most part in the nonpolar fraction, principally as promazine sulfoxide and nor1promazine sulfoxide, while rabbits tend to excrete the drug as free or conjugated phenols. The major rabbit metabolite, 3-hydroxyproma-zine, is distributed among all 3 phenol fractions. Neither animal produces primary amine metabolites in amounts comparable to man. Addendum. The peach factor (Pe) has recently been identified in our laboratory as phenothiazine sulfoxide. This indicates that both man and dog can degrade the side chain of promazine down to the phenothiazine nucleus. Orc appears to be an oxidation product derived from 3-hydroxyphenothiazine. Chlor-promazine yields the corresponding 2-chloro derivatives as metabolites. Appreciation is expressed to Dr. Herbert S. Posner, St. Elizabeths Hospital, Washington, D.C., for 4 isomeric hydroxypromazine standards, and to Wyeth Laboratories for promazine, nor1promazine, nor2-promazine and promazine sulfoxide.