The elimination of [3H]pafenolol and metabolites was investigated in fasted and fed rats. Separate groups received intravenous doses (0.3 and 3.0 mumol/kg) and oral doses (1 and 25 mumol/kg). After iv administration of pafenolol, the excretion of unchanged drug into urine and feces was about 50 and 25-30% of the given dose, respectively. The predominating mechanism for the excretion of pafenolol into feces was intestinal excretion (exsorption) directly from blood into gut lumen, since only about 3% of a given iv dose was recovered as pafenolol in the bile. When the oral dose was raised from 1 to 25 mumol/kg, the mean (+/- SD) bioavailability, calculated from urine data, increased from 14 +/- 9 to 30 +/- 11% (P < 0.05) in the starved rats and from 14 +/- 3 to 16 +/- 3% in the fed animals. In parallel, the fraction absorbed from the gut (fa) increased from 19 +/- 9 to 31 +/- 10% in the starved rats and from 16 +/- 4 to 19 +/- 5% in the fed animals, respectively. This indicates that the low bioavailability is due primarily to poor intestinal uptake.