Tissue water content was determined by desiccation to constant weight at 40 degrees-50 degrees C in 14 tissues from two groups of rats weighing 200-250 and 270-430 g, respectively. The water content (mean +/- SE; ml/g) was highest in testes (0.861 +/- 0.002) and lowest in adipose (0.183 +/- 0.017) followed by bone (0.446 +/- 0.017) and skin (0.651 +/- 0.007). The average water content in the remaining tissues was 0.763 (+/- 0.003). Upon correction for the water content of residual tissue blood, significant difference between the uncorrected and corrected tissue water was observed for spleen, lungs, kidneys, heart, liver, and brain. Tissue water was independent of body weight, and was the same for right and left kidneys as well as testes and bone. Whereas the position of the muscle (back, abdomen, hindlimb) and adipose tissue (perirenal and subcutaneous) had no influence on water content, for skin, a slight difference was found between back and abdomen. In general, the current results are in agreement with composite literature values, but provide in one study data for all tissues used in the development of physiologically based pharmacokinetic models of rat.