Phosphonate compounds are of considerable interest because of their effects on biological mineralization and mineral metabolism. The effects of graded doses given parenterally or orally of N,N,N',N'-ethylenediamine tetramethylene phosphonic acid (EDITEMPA) on calcium absorption, plasma calcium, endochondral bone elongation, and osseous tissue histology of rats were determined. In some experiments 1-hydroxyethylidene-1,1-bisphosphonic acid (HEBP) was included for comparison. Given sc for 7 days, EDITEMPA caused dose-related decreases in net weight gain, intestinal calcium absorption, and longitudinal bone growth. There were also increases in total plasma calcium concentrations and excess osteoid accumulation in bone. When EDITEMPA was given po for 7, 28, or 90 days, few changes in osseous tissues were observed and then only at the highest dose (333 mg/kg/day). An equivalent dose of HEBP caused substantial changes in osseous tissues and calcium parameters.