1. Quantitative determinations of unchanged diclofenac and two of its major phenolic metabolites were made by reverse isotope dilution analysis on urine of rat, dog, rhesus monkey, baboon and man and on bile of rat, dog and man. Isotope dilution analysis was performed before and after various methods of enzymic and chemical hydrolysis. 2. The same samples were also analysed by two-dimensional t.l.c. and subsequent autoradiography, to estimate the remaining phenolic metabolites. 3. In contrast to rat, rhesus monkey, baboon and man, which excrete mainly hydroxylated metabolites, the dog does not oxidize diclofenac. Dog urine contained a relatively stable taurine conjugate of diclofenac, and in the bile an ester glucuronide was excreted, which decomposed even in weakly alkaline soln. 4. The unstable ester glucuronide found in dog bile was also demonstrable in rat bile. It presumably hydrolyses in the duodenum, releasing diclofenac which undergoes enterohepatic circulation.