1 . Normal and diseased bone was obtained by biopsy from five patients suffering from Paget's disease. The tissue was studied by histology, microradiography and quantitative fluorescence microscopy using tetracycline markers. Study of the morphological changes showed that two of the biopsies could be regarded as normal, while one was osteoporotic; two biopsy specimens were in the porotic phase of Paget's disease and the remaining five were in the sclerotic phase.

2. The tetracycline markers were used to measure the linear rate at which bone was deposited on individual surfaces (appositional growth rate) in µ per day and the percentage volume of new bone added to the total volume of bone per day (bone formation rate). The values obtained for appositional growth rate in all the biopsies were of the order of 1 µ per day, but slightly higher values were obtained in the diseased tissue of each individual. The bone formation rate in normal bone from the proximal femur was about 0·04 per cent per day, about 0·13 per cent per day in the porotic phase, and about 0·4 per cent per day in the sclerotic phase of Paget's disease.

3. Although these values must be accepted with some reservation, there seems to be no doubt that there is an upper limit of about 1 µ per day to the rate of deposition of bone on an individual bone surface; this suggests that in Paget's disease the osteoblast behaves as a normal cell.

1. In two dogs, approximately one to two years and three to four months of age, an experimental comparison was made between the calcium accretion rate as defined by the Bauer-Carlsson-Lindquist equation, and the bone formation rate determined by double tetracycline labelling.

2. The overall calcium accretion rate was determined from the specific activity of the blood plasma, and the urinary and faecal excretion of isotope, following an intravenous tracer dose of Ca⁴⁵. A time of five days after injection was used for the calculation of accretion rates, but data for shorter times of calculation are included.

3. Local accretion rates were obtained for different parts of the skeleton by determining the specific activities of bone samples at the end of the experiment.

4. The amount of isotope the uptake of which was not related to new bone formation (the diffuse component) was determined autoradiographically.

5. Local values for appositional growth rate and bone formation rate were obtained, using sections of undecalcified bone specimens, by measuring the linear separation between two tetracycline bone markers and the area of new bone enclosed by them.

6. In the older dog, the measurements for cortical bone showed that the accretion rate was two to three times as great as the bone formation rate: the observed diffuse component was sufficient to account for the greater part of this difference. Measurement of the bone formation rate for cancellous bone presented difficulties, but the approximate values obtained suggested that the accretion rate and the bone formation rate were of about the same order for this tissue.

7. In the younger dog, the bone formation rate could be determined only in cortical bone: at the sites studied, the values for the accretion rate and the bone formation rate did not differ by more than 20 per cent. It is suggested that this is due partly to the low specific activity of the diffuse component in this young animal, and partly to the relatively large amounts of new bone formed during the period of the experiment.

8. Despite the important differences between the rates of calcium accretion and bone formation that were found to exist in regions where there was only a small amount of new bone formation, there was a strong correlation between the two rates. The value of the accretion rate as a parameter of bone metabolism is clear.