Four normal volunteers each received two intravenous doses of PA. The mean low dose was 3.30 mg kg-1 (infused over 20 minutes) while the mean high dose was 12.5 mg kg-1 (infused over 60 minutes). Blood samples were collected for 12 hours and urine was collected for 48 hours after each dose. PA concentrations were determined by both HPLC and fluorescent immunoassay methods. The reported concentrations and pharmacokinetic parameters are from the HPLC data unless otherwise indicated. The mean peak serum PA concentrations resulting from the low and high doses were 3.18 and 9.07 micrograms ml-1, respectively. Total PA clearance averaged 763 ml min-1 and 577 ml min-1 while renal clearance averaged 360 ml min-1 and 318 ml min-1 after the low and high doses, respectively. Concentration-dependent decreases in nonrenal PA clearance ranged from 31 to 43 percent (p less than 0.05) in the four subjects. Total clearance decreases ranged from 4.7 to 36 per cent (p less than 0.05). Differences between doses in renal clearance, elimination rate constant, and volume of distribution were not statistically significant. This study demonstrates that the nonrenal and total clearances of PA are concentration-dependent in normal subjects at therapeutic plasma PA concentrations and suggests that the total clearance changes are of sufficient magnitude to be clinically important.