Considerable progress is being made in the development of non-radioactive microsphere methods. Validation studies of the three commercially available non-radioactive microspheres are promising. In most experimental conditions the use of non-radioactive microspheres saves money. Avoiding the use of radioactivity facilitates the use of microspheres in chronic animal experiments and when blood flow and chemical measurements are performed in the same sample. Moreover, using histological techniques, distributions of coloured or fluorescent microspheres in subunits of organs could be quantified, opening new scientific possibilities. Currently, the fluorescent microsphere technique seems to be the most promising non-radioactive microsphere method. Due to the high sensitivity and good spectral separation, the number of microspheres injected can be as small as that used, for radioactive microspheres, at least six labels can be used, and the relatively large volume in which fluorescence is measured (approximately 1-3 ml) enables the use of time saving microsphere isolation techniques. Development of these methods and further automation of the quantification process (using either automised spectrometry or FACS analysis) will considerably increase interest in the non-radioactive microsphere techniques. To accelerate these developments, investigators are encouraged to share their experiences.