Recent studies have shown that in situ PCO2 in rat renal cortical structures far exceeds systemic arterial PCO2. These results were opposite to previous assumptions that renal proximal tubule fluid PCO2 approximated arterial PCO2. The present studies examined the species and organ specificity of the elevated PCO2 in 39 New Zealand White rabbits studied under normal acid-base conditions. In situ PCO2 was measured in renal cortex, superficial hepatic parenchyma, skeletal muscle, superficial cerebral cortex, and femoral nerve, artery, and vein. The results showed rabbit renal cortical PCO2 (57.2 +/- 1.2 mmHg) to be higher than both systemic arterial (39.1 +/- 2.0 mmHg) and venous PCO2 (45.4 +/- 2.1 mmHg). Similarly, liver PCO2 (64.1 +/- 3.5 mmHg) was found to be significantly higher than systemic arterial and venous PCO2 and also higher than portal and hepatic vein PCO2. Skeletal muscle, cerebral cortex, and femoral nerve PCO2 levels were usually greater than systemic arterial PCO2 but less than systemic venous PCO2. These observations show that in situ PCO2 is significantly elevated above afferent and efferent blood PCO2 in the kidney and liver but not in muscle or brain. A possible explanation for these findings in the former two organs may be high CO2 production and/or trapping of CO2 by their vascular systems.