The aim of this study was to build a population biokinetic model for the uptake and retention of radioiodine in the thyroid of hyperthyroid patients. At Malmö University Hospital (Malmö, Sweden), a database with detailed information from (131)I-iodide therapies has been created. The database consisted of uptake measurement from 422 patients with the diagnoses of diffuse goiter, multinodular goiter, adenoma, and undefined. In total, 2013 uptake measurements, performed from 3 hours to 9 days after intake of a test activity of (131)I, were included. Nonlinear mixed effect modeling (NLME) was used to model the population biokinetics of (131)I. The structural model was parameterized in terms of the level of uptake (A), the rate constant for the absorption to the thyroid (k(a)) and the rate constant for the output from the thyroid (k(e)). Interindividual and interoccasion variabilities were added to all three structural parameters. The following covariates were found to significantly affect the structural model parameters: Diagnosis on A, k(a) and K(e), volume of the thyroid on A and k(a), and age on k(a) and k(e). The interindividual and interoccasion variabilities were in the range of 8%-28%. The variance of the residual error, modeled as an additive, was low. This type of modeling is a powerful tool for biokinetic studies and should be used in other biokinetic areas of radioiodine therapy, such as radiation dosimetry.