A small proportion of radiopharmaceutical administrations are extravasted from the injection site to the surrounding tissue. Of interest is the resulting absorbed dose. This investigation was undertaken to determine the biologic behavior and subsequent dosimetry of selected radiopharmaceutical infiltrations using a rat model. Subcutaneous injection of 99mTc-microspheres, 99mTc-MDP, 67Ga-citrate, and 201Tl-chloride were studied. Three adult male Sprague-Dawley rats were injected subcutaneously at three separate sites on the shaven backs of the animals for each agent studied (i.e., nine sites per agent). The rats were imaged and the resulting data were analyzed by computer immediately after injection and at various intervals up to 5-6 h, and again at 24 h. Particulate subcutaneous 99mTc-microspheres exhibit essentially no diffusion of tracer from the injection site, whereas non particulates showed a biexponential release pattern. Radiation burdens in rad/mCi (mGy/MBq) due to an infiltrate volume uniformally distributed over a 5 g mass for 99mTc-microspheres, 99mTc-MDP, 67Ga-citrate and 201Tl-chloride were 59.4(16.0), 13.6(3.7), 32.9(8.9) and 92.2(24.9), respectively. The radiobiological risk associated with these radiation burdens are below that needed to produce severe skin reactions when distributed within a 5 g mass.