Absorption, distribution, metabolism and excretion studies with gamma-oxo-(1,1'-biphenyl)-4-butanoic acid (fenbufen) have been conducted in several laboratory animal species. Single oral doses of 14C-fenbufen were administered to rats, guinea pigs, rabbits and dogs (10, 40 and 100 mg/kg) and to mice and monkeys (40 and 100 mg/kg); rats, rabbits and dogs received an i.v. dose of 10 mg/kg. Multiple oral doses of 40 mg/kg of non-radiolabelled fenbufen were studied in the rat and dog. Plasma concentrations of fenbufen and its metabolites were dose dependent with areas under the curve showing general linearity both within and among species over the range studied (10--100 mg/kg). Radioactivity was present in all tissues examined following a dose of 10 mg/kg 14C-fenbufen orally to rats and guinea pigs. Except for gastrointestinal tract, liver and kidney these tissue levels were usually lower than the corresponding plasma level through 24 h post dose. The major drug-related material in plasma of the rat, guinea pig and dog was (1,1'-biphenyl)-4-acetic acid; in the monkey it was gamma-hydroxy(1,1'-biphenyl)-4-butanoic acid. These two compounds together with unchanged fenbufen were present in the plasma of all the animals studied. In addition 4'-hydroxy(1,1'-biphenyl)-4-acetic acid was found in rat plasma and beta, gamma-dihydroxyl(1,1'-biphenyl)-4-butanoic acid in dog plasma. The plasma profiles of fenbufen and metabolites did not change during multiple, daily oral doses of 40 mg/kg in either the rat (up to 10 days) or the dog through 18 months. In varying proportions, a total of 11 metabolites (including those listed above) together with fenbufen itself were isolated and characterized from the urine of mice, rats, guinea pigs, dogs and/or monkeys dosed with fenbufen. Within each of the species studied, excretion patterns of drug-related materials in the urine and feces following an i.v. dose were similar to those following the oral doses. In general urine was the major excretory pathway.