Clinical usefulness and factors affecting transcutaneous CO2(PtcCO2) monitoring were studied in 22 critically ill neonates. In 10 of 22 infants, both tissue pH (pHt) and PtcCO2were monitored simultaneously using Roche pHtand CO2electrodes. Arterial blood gases were obtained from umbilical artery catheter. The effect of variations in blood pressure, oxygenation, arterial pH (pHa) pHt, and medications on PtcCO2were studied.There was a linear correlation between pHtand pHa(n = 108, r = 0.85, slope 1.08), PtcCO2and PaCO2(n = 188, r = 0.85, slope 1.49). The pHtchanges correlated better with PtcCO2than with arterial CO2(r = 0.78, slope 1.35).The major factors affecting the PtcCO2relationship were (a) hypoxia and (b) acidosis. When PaO2< 40 torr, PtcCO2correlated poorly to PaCO2(n = 23, r = 0.48, slope 0.72) whereas, during normoxia (PaO2> 40 torr), it correlated well, r = 0.85, slope 1.51 similarly. When pHtwas > 7.30, PtcCO2correlated better with PaCO2(r = 0.88, slope 1.37) than during tissue acidosis (r = 0.71, slope 1.51). Mean blood pressure down to 30 mm Hg and administration of dopamine and tolazoline did not affect the PtcCO2to PaCO2relationship (n = 69, r = 0.86, slope 1.6).Clinically, both continuous pHtand PtcCO2were found to be very useful in the management of critically ill neonates.