Metabolism of water-soluble synthetic corticosteroid esters, hydrocortisone hemisuccinate (H-H); hydrocortisone phosphate (HP), prednisolone hemisuccinate (P-H), prednisolone phosphate (P-P), dexamethasone phosphate (D-P) and dexamethasone sulfate (D-S) was studied by i.v. administration of steroids in a dose of 100 mg to 6 healthy volunteers and consequtive urine collections over 24 hrs. Uniary metabolites were separated into free, glucuronide, sulfate and "unhydrolyzed" fractions and measured by means of Porter-Silber (P-S) reaction and isonicotinic acid (INH) reaction. In H-H, H-P and D-S, glucuronide conjugates constituted the largest fraction of P-S positive metabolites in 24 hr-urine. In contrast, P-H, P-P and D-P were excreted mainly as free metabolites. Small but variable portions were found as sulfate and "unhydrolized" conjugates. Time course study revealed that, in H-H, H-P and D-S, the free/glucuronide ratio of P-S positive metabolites decreased progressively or remained low throughout the collection periods, whereas in P-H, P-P and D-P the ratio increased markedly in the 4--12 hr period. For all steroids, the INH/P-S ratio was found to be high in the free fraction and low in the glucuronide fraction; the tendency was especially marked in P-H, P-P and d-p. INH-positive metabolites were also predominant in the sulfate and "unhydrolyzed" fractions. The results indicate that the metabolism of synthetic corticosteroids, in general, is characterized by diminised rate of ring A reduction followed by glucuronide conjugation and compensatory increase in free metabolites, the bulk of which consists of ring A intact, C-20 reduced metabolites. 6-Hydroxylated metabolites may also be increased. Conjugation with sulfuric acid occurs but to a small extent. The consistent presence of "unhydrolyzed" metabolites suggests that portions of esters can be excreted unsplitted. It is also noted that the structure of steroid moieties and type of esters were important factors determining the quantitative and qualitative difference in their metabolic fates.