A glucose concentration analysis of human whole blood samples has been accomplished using pulsed laser photoacoustic spectroscopy (LPAS). Using a CO2 laser operating with microJ pulse energies, the technique has shown the required discrimination and sensitivity to determine glucose concentrations within the physiological range (18-450 mg dl-1) in whole blood samples. The sensitivity achieved with this system is comparable to that of the existing commercial enzyme-based diagnostic systems presently used in hospital clinical chemistry environments. The technique is compared with other optical methods that have recently been used for glucose determination, and its applicability for use in the development of an in vivo monitor is discussed.