Summary:The methods described in the literature for pH determination in human erythrocytes, i.e. the direct potentiometric measurement of haemolysed erythrocytes and the 5,5-dimethyl-2,4-oxazolidinedione (DMO) method, were examined and compared. In spite of careful optimization of the experimental technique, a statistically significant difference of a few hundredths of a pH unit remained between the results of the two methods. The calculation of the cellular water space of the erythrocytes is suggested äs a possible reason for this difference; in the DMO method this leads to uncertainty in the determination of the DMO concentration and therefore in the derived intracellular pH values. For clinical use, the direct pH measurement of haemolysed erythrocytes, using the technique described here, is recommended.