A gamma-ray detector system used in conjunction with isolated vascularly perfused rabbit septa labeled with the Ca-like cations 85Sr and 133Ba has been developed to test the feasibility of constructing a considerably more efficient detector system capable of measuring the highly energetic (Emax congruent to 1.3 MeV) 47Ca radionuclide. In addition an experimental design has been developed to quantify, statistically, perturbations of total tissue Ca, Sr, or Ba should they occur. This project was undertaken because the severe attenuation by living tissue of the beta-emitting radionuclide 45Ca (Emax congruent to 250 keV) limits its usefulness as a Ca tracer during experiments in which total tissue Ca is being measured minute-by-minute by an external detector. Analyses of over 100 experiments conducted on 35Sr- and 133Ba-labeled rabbit septa indicate that a tissue-detector system can be developed having the capacity to resolve perturbations of as little as 2 mumol Ca/kg wet tissue at 1-min sampling times or 6 mumol Ca/kg wet tissue at 0.1-min sampling times.