The present experiments were carried out to elucidate the chemical structure and the pharmacological activity of the main metabolites of picumast (3,4-dimethyl-7-[4-(4-chlorobenzyl)piperazine-1-yl]propoxycoumarin ). The metabolic pathways were identical in animals and man, but there were major quantitative differences. The fraction of the radioactivity in the plasma attributable to the parent compound 0.5 to 3 h after oral administration of picumast dihydrochloride was less than 15% in animals but 95% to 57% in man. Inhibition of the C3-zymosan-induced chemilumiescence of human leucocytes was taken as an indicator of the diminished liberation of mediators and inhibition of the histamine-induced contraction of isolated guinea-pig lung strips as an example for the antagonism of picumast dihydrochloride to mediators of allergic reactions. Stepwise oxidation of the 3-methyl substituent of the coumarin ring to the alcohol and the carbonic acid increased the histaminolytic potency, but decreased the inhibition of chemiluminescence. Another metabolite formed by cleavage of the piperazine-containing side chain was inactive in both tests.