Transfer functions of 99mTc methylene diphosphonate (MDP), 99mTc 2,3-dicarboxypropane-1,1-diphosphonate (DPD) and 99mTc ethane-1-hydroxy-1,1-diphosphonate (EHDP) into bone and extravascular fluid of soft tissues were determined in 5 dogs by deconvolution analysis of the time-course of plasma, soft tissue and bone radioactivity. The transfer rates 5 min after injection--indicating the rapid exchange of the tracer between plasma and the extravascular fluid--decrease in the order MDP greater than EHDP greater than DPD (P less than 0.05). The transfer rates into bone--determined from transfer rates between 30 and 60 min--decreased in a different order, i.e. MDP greater than DPD greater than EHDP (P less than 0.05). The fractional bone uptake of diphosphonates estimated from the ratio of early to late transfer rates was slightly greater for DPD than for MDP and EHDP respectively. The difference between DPD and MDP was not significant (P greater than 0.05). The average bone and soft tissue concentrations of DPD 60 min after injection were greater than that of MDP and EHDP due to different plasma concentrations (DPD greater than EHDP greater than MDP), whereas the bone-to-soft tissue ratios decreased in the sequence MDP greater than DPD greater than EHDP (P less than 0.05).--Our results reveal different biokinetics of MDP, DPD and EHDP explaining variations in osseous and soft tissue uptake suggesting that deconvolution analysis could play an important role in bone scan interpretation.