Single oral doses of 600 mg of 14C-labelled gamma-oxo(1,1'-biphenyl)-4-butanoic acid (fenbufen) were administered to three male volunteers. Additional male and female subjects received single (500-700 mg) or multiple (300-400 mg b.i.d.) doses of non-isotopically labelled drug. Fenbufen was rapidly absorbed from the gastroiintestinal tract to the extent of at least 78%. Food reduced the rate but not the extent of absorption. Peak serum concentrations of total drug related compounds were reached by 2 h, at which time fenbufen accounted for only 11% of these substances. The remaining drug related material consisted of two metabolites: gamma-hydroxy(1,1'-biphenyl)-4-butanoic acid and (1,1'-biphenyl)-4-acetic acid. Steady state serum concentrations were reached within a week with multiple dosing regimens. The ratio of fenbufen to its circulating metabolites did not change over a month of daily dosing. Only traces of fenbufen and metabolites were present in the cellular components of blood or in human milk, but significant amounts (concentrations one-third those in serum) were measured in the synovial fluid of arthritic patients. Fenbufen and its circulating metabolites were highly bound (> 98%) to human serum in vitro, but at therapeutic levels showed very small or no effects on the serum binding of various other commonly used drugs. Concomitant administration of fenbufen and acetylsalicylic acid (ASA) resulted in decreased serum concentration of fenbufen and its metabolites compared to those obtained from fenbufen administration alone. In addition to the serum metabolites, three more transformation products were identified in urine: 4'-hydroxy(1,1'-biphenyl)-4-acetic acid, gamma,4'-dihydroxy(1,1'-biphenyl)-4-butanoic acid and beta, gamma-dyhydroxy(1,1'-biphenyl)-4-butanoic acid.