We have undertaken an experimental examination of the conventional internal dosimetry assumptions of homogeneity of radionuclide deposition in tissues. The distribution of radiolabeled Microlite has been quantitated in mouse liver at the millimeter (multicellular) and the micrometer (cellular) levels. Measurements of radioactivity in 1-mm3 tissue samples indicate homogeneous radionuclide distribution; those derived from autoradiographs of 0.5-micron tissue sections show that, relative to other cells, the colloid was concentrated 200- to 1000-fold in liver macrophages. The dosimetric implications of such inhomogeneous radionuclide distribution in human liver, where similar radionuclide distribution is expected, are discussed on the basis of a recently developed model for calculating the dose at the cellular level, and the estimates are compared to conventional internal dosimetry predictions. It is demonstrated that during routine diagnostic examinations with 99mTc-Microlite, conventional dosimetry underestimates the dose to labeled human liver cells by factors of 8-30.