The biodistribution and infection imaging properties of a 99mTc labeled hydrazino nicotinamide (HYNIC) derivatized chemotactic peptide analog (For-Met-Leu-Phe-Lys-HYNIC) and 111In-DTPA-IgG were compared in rabbits with Escherichia coli infection. Six New Zealand white rabbits were injected in the left posterior thigh with a suspension of E. coli. Twenty four hours later, the animals were injected with: 1.0 mCi of 99mTc labeled peptide plus 0.1 mCi of 111In-DTPA-IgG. At 2-3 and 16-18 h, dual photon scintigrams were acquired and the images were corrected for crossover between the two windows. After recording the final images, the animals were sacrificed and biodistribution was determined. At both imaging times the biodistributions of the two reagents were markedly different. The highest concentrations of 111In-DTPA-IgG were detected in blood pool structures, liver and kidney. In contrast localization of 99mTc labeled peptide was greatest in spleen, lung and liver (consistent with binding to leukocytes). In general, the sites of infection were better visualized with the radiolabeled peptide and T/B ratios increased with time (P < 0.01). At both times, the T/Bs for 99mTc-peptide were higher (P < 0.01); 3.54 +/- 0.47 vs 2.52 +/- 0.38 at 2-3 h and 6.88 +/- 0.79 vs 3.78 +/- 0.36 at 16-18 h. These results indicate that although both radiopharmaceuticals localize at sites of infection, the radiolabeled peptide are superior reagents for the rapid detection of focal sites of infection. However, since the mechanisms of localization are different the combined use of both agents could have value in the general evaluation of infection/inflammation.