Dental amalgam is the major source of inorganic mercury (Hg) exposure in the general population. The objective of the present study was to obtain data on changes in Hg levels in blood, plasma, and urine following removal of all amalgam fillings during one dental session in 12 healthy subjects. The mean number of amalgam surfaces was 18 (range, 13 to 34). Frequent blood sampling and 24-hour urine collections were performed up to 115 days after amalgam removal, and in eight subjects additional samples of plasma and urine were collected up to three years after amalgam removal. A transient increase of Hg concentrations in blood and plasma was observed within 48 hours after amalgam removal. In plasma, the peak concentrations significantly exceeded the pre-removal plasma Hg levels by, on average, 32% (1.3 nmol/L; range, 0.1 to 4.2). No increase in the urinary Hg excretion rate was apparent after amalgam removal. An exponential decline of Hg was seen in all media. Sixty days after the amalgam removal, the Hg levels in blood, plasma, and urine had declined to approximately 60% of the pre-removal levels. In seven subjects, who were followed for up to three years, the half-lives of Hg in plasma and urine were calculated. In plasma, a bi-exponential model was applied, and the half-life was estimated at median 88 days (range, 21 to 121). The kinetics of Hg in urine (nmol/24 hrs) fit a mono-exponential model with a median half-life of 46 days (range, 35 to 67). It is concluded that the process of removing amalgam fillings can have a considerable impact on Hg levels in biological fluids. After removal, there was a considerable decline in the Hg levels of blood, plasma, and urine, which slowly approached those of subjects without any history of amalgam fillings.