The aim of the present study was to determine whether acute changes in blood gases and pH alter sulfamethazine (SMZ) kinetics. Groups of conscious rabbits were exposed for 270 min either to air or to a high CO2 and (or) low O2 atmosphere to produce hypercapnia, hypoxemia, or both. Another group of rabbits received 47 mL/kg of 0.3 M HCl by gavage tube to induce metabolic acidosis. Once the blood gases were stabilized, the rabbits received 20 mg/kg SMZ i.v. Multiple blood samples were drawn for 180 min to assess SMZ kinetic parameters, SMZ protein binding, and blood gases. Fifteen minutes after the administration of SMZ, a suboccipital puncture was performed to determine the concentration of SMZ in the cerebrospinal fluid (CSF). Urine was collected for the first 180 min through a sterile catheter and for the next 21 h in a metabolic cage. Hypercapnia alone did not significantly influence SMZ kinetics. Hypoxemia, hypoxemia combined with hypercapnia, and metabolic acidosis increased the SMZ apparent volume of distribution (V) and total body clearance (CL). This increase in the SMZ V correlated positively (p less than 0.01) to the ratio of SMZ concentration in CSF to SMZ concentration in plasma. The increase in SMZ CL was mainly due to an increase in nonrenal clearance, although a slight increase in SMZ renal clearance was also observed.(ABSTRACT TRUNCATED AT 250 WORDS)