The purpose of this study was to evaluate the role of both protein and radionuclide in the accumulation of 111In-labeled human immunoglobulin G (IgG) in infectious foci. In rats with a calf muscle infection, biodistribution was determined 2, 6, 24, and 48 hr after injection of a radiopharmaceutical. For IgG, human serum albumin (HSA) and human immunoglobulin A (IgA), all labeled with 111In, target-to-background (T/B) ratios were similar throughout the study. However, absolute abscess uptake of 111In-IgA was significantly lower. For IgG labeled with 111In, 123I, or 99mTc, similar T/B ratios were found up to 24 hr. After 48 hr, the T/B ratio of 111In-IgG was significantly higher than the T/B ratio of 123I-IgG. The absolute abscess uptake of 111In-IgG was higher than that of 99mTc-IgG at 24 hr and 123I-IgG at 48 hr. In conclusion, the radionuclide appears to be of major importance in the accumulation of radiolabeled proteins in infectious foci. Protein mainly influences blood clearance and distribution in organs. The Fc-gamma receptor is not crucial for accumulation in infectious foci.