A graphite furnace atomic absorption spectrometry method has been developed for the quantitative determination of submicromolar endogenous concentration of lithium in human plasma and urine using pyrolitically-coated graphite tubes in combination with ammonium nitrate matrix modification. This latter treatment could not completely abolish the interferences caused by the matrix, notably in urine samples. The variability of the urinary matrices required an additional standardization procedure by solid-phase extraction on strongly acidic cation exchange cartridges. Matrix-matched samples were used for the establishment of calibration curves with the addition-calibration method. Calibration curves were linear up to 0.72 mumol/l (1.0 > r2 > 0.99). The described method enables accurate measurements of trace-lithium in biological samples at concentrations down to 0.03 mumol/l with intra- and inter-day variabilities < 10%. The method was applied to the determination of trace-lithium levels in urine and plasma samples from healthy individuals enabling the calculation of its fractional excretion (FeLi) (median range 17.3%), a value which reflects the functional capacity of the kidney to reabsorb sodium and water at the proximal tubular portion of the nephron. This sensitive method can thus be used as an investigative and diagnostic tool in various renal pathophysiological conditions, in clinical research, and may also be applied to studies on the trace-lithium status of population in connection with psycho-affective disorders.