Changes in glomerular volume (V(glom)) play an important role in the initiation and progression of various glomerulopathies. Estimation of V(glom) in the normal kidney provides baseline values for studies of glomerular hypertrophy in disease. The traditional model-based method of Weibel and Gomez is widely applied to estimate V(glom) in clinical biopsy specimens. Assumptions of glomerular size distribution and shape required by this method are potential sources of bias that have not been verified. We evaluated the applicability of the glomerular size distribution coefficient in estimating V(glom) in human kidneys. V(glom) of 720 non-sclerotic glomeruli in histologically normal kidneys of 24 males (20-69 years) was estimated by the unbiased disector/Cavalieri approach. Accurate glomerular diameters were calculated from Cavalieri estimates of V(glom) assuming glomerular sphericity. The coefficients of variation (CV) of glomerular diameters were compared with the corresponding values of the size distribution coefficient predicted by the Weibel and Gomez method. Mean (SD) glomerular diameter was 201 (28) mm (range 110-276 mm). The CV of glomerular diameter within each kidney ranged from 4.9 to 14.6%. Corresponding glomerular size distribution coefficients predicted by the formula of Weibel and Gomez ranged from 1.00 to just 1.03. The value of the size distribution coefficient required by the Weibel and Gomez technique when estimating V(glom) in normal human kidneys is remarkably constant. This is despite large variations in V(glom). Future studies should examine the extent of bias introduced by the glomerular shape assumptions of this method.