A fluorescence-based fiber optic measurement system has been developed for monitoring pH, pCO2, and pO2 through a 20-gauge radial artery catheter without compromising capabilities for monitoring arterial pressure or for blood withdrawal. The measuring probe consists of three optical fibers to which the sensing chemistries are attached, and a thermocouple that measures temperature. The probe is designed to meet in-vivo biocompatibility requirements for a one-time use of up to 72 h. The components that are in contact with the patient's blood are nontoxic, nonhemolytic, nonthrombogenic, and sterilizable. Blood compatibility is enhanced by including covalently bound heparin. The in-vitro accuracy of the system has been tested against commercial blood-gas measurement instruments; comparison with tonometry and blood gas values gave r greater than or equal to 0.98 for all three sensors. The standard error for all sensors was within the College of American Pathologists' accuracy guidelines for measuring blood gas. Instrumental drift was minimal, indicating that system performance characteristics should not be the limiting factor in obtaining clinically useful information for up to 72 h. The response times of the sensors in animal and in-vitro studies were less than 2 min, suitable for monitoring physiological changes in blood gas values.