Radiation-induced skeletal changes were studied in beagles fed from midgestation to 1.5 yr of age diets containing SOSrC12 in equilibrium with or administered 226RaC12 in 8 semimonthly i.v. injections starting at 2,4 or 14 months of age. Skeletal changes were evaluated with a radiographic X-ray scoring system in 20 skeletal regions; each region was scored on a 0-6 scale. Skeletal changes were endosteal or periosteal cortical sclerosis and thickening (ECST, POCST), fractures, osteolytic lesions and trabecular coarsening. I n general, a lower level of skeletal changes were observed in + SOY relative to 226Ra labeled skeletons.Changes in goSr-labeled skeletons were observed for average daily ingestions larger than 1.5 pCi At 36 pCi 90Sr + goY/day diet, the highest ingested activity level in this experiment, ECST and POCST were observed in 100 and 50 % of all dogs, respectively. 226Ra induced skeletal changes were minimal for total injectivityAo = 0.53 pCi 226Ra. ECST incidence in at least one of the 20 skeletal regions was 100 %for dogs injected A, 2 9.3 pCi 2z6Ra, POCST incidence was 100 only at A, 2 83.6 pCi z26Ra. Fractures were observed at A, 2 14 pCi 226Ra. Total skeletal changes and rate of changes were analyzed as a function of $%r + and zz6Ra dose rate, dose and time. At accumulated doses of 90Sr + less than D = 7 krad, the degree and rate of skeletal changes were about the same, but for larger than 7 krad a definite dose rate dependence was observed. For equivalent doses ofradium, skeletal changes were larger at lower injected activity levels. Implications of dose rate, dose and time effects on response surface for extrapolation of experimental animal data to man are discussed. +