Atomic absorption spectrophotometry offers a method applicable to the determination of serum manganese in clinical research. The signal-to-noise ratio is great enough to yield precise data even with 10X scale expansion. The method has the required sensitivity for the measurement of the concentrations encountered in human serum, even though the signals produced are very small. It requires a few manipulative steps, and the possibility of contamination is kept to a minimum. Interference from other materials usually present in the matrix does not present a problem. The mean manganese concentration in the serum of normal fasting human subjects was 2.4 ± 0.7 µg/100 ml without any variation between the sexes. The concentration in the same individual does not vary over long periods of time. Initial observations do not indicate diurnal variation. Large quantities of manganese administered to two normal individuals for 3 and 8 weeks, respectively, did not produce a detectable change in the serum manganese concentrations. Studies are underway to adapt the method to the determination of manganese in blood cells and other tissues.