The accumulation of nonspecific polyclonal human immunoglobulin (IgG) radiolabeled with 125I or 111In was compared to that of [67Ga]citrate and [99mTc]albumin in rats with deep thigh inflammation due to Escherichia coli infection. Serial scintigrams were acquired at 1, 3, 24, and in some cases, 48 hr after injection. As early as 3 hr postinjection, [111In]IgG showed greater accumulation at the lesion than [99mTc]HSA (p less than 0.01). Both [125I]IgG and [111In]IgG showed greater accumulation than [67Ga]citrate (p less than 0.01). At 24 hr, IgG image definition increased, while HSA image definition decreased, and the intensity of accumulation of both IgG preparations was greater than that of [67Ga]citrate or [99mTc]HSA (p less than 0.01). At all imaging times, [67Ga]citrate accumulation was surprisingly low. In inflammation produced by Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, or turpentine, [111In]IgG accumulation was similar to the results obtained with Escherichia coli. These studies suggest that focal sites of inflammation can be detected with radiolabeled nonspecific human polyclonal IgG.