One male volunteer received a single oral dose of 400 mg of 14C-labelled phenylbutazone (Butazolidin) and a second volunteer a repeated oral dose of 3 X 400 mg. The absorption from the gastro-intestinal tract was found to be rapid and complete. The integrated concentration of unchanged phenylbutazone in plasma, as estimated from the area under the concentration curve (AUC) between 0 and 336 h, was 63% of that of total 14C-substances. The corresponding AUC of three specifically determined metabolites, i.e. oxyphenbutazone, gamma-hydroxyphenylbutazone and p,gamma-dihydroxyphenylbutazone were 23%, 2% and 0.5%, respectively. A single oral dose was slowly excreted from the organism, since within 21 days only 88% was recovered, 61% from urine and 27% from faeces. About 1% of total urinary radioactivity was excreted as unchanged drug. The sum of specifically measured metabolites (oxyphenbutazone, gamma-hydroxyphenylbutazone, p,gamma-dihydroxyphenylbutazone) and phenylbutazone in urine did not cover more than about 10%. Solely oxyphenbutazone was present as an O-glucuronide, but only in small amounts. About 40% and 12% of total urinary radioactivity was due to C(4)-glucuronides of phenylbutazone and gamma-hydroxyphenylbutazone, respectively. Their structures were established by spectroscopic means. These metabolites contain pyrazolidine rings directly attached to glucuronic acid via a C-C bond, thus representing a novel class of drug metabolites.