The present series of experiments was designed to compare 99mTc with 51Cr as a lymphocyte label in rabbits and to correlate organ distribution patterns as determined by postmortem counting with those observed by 99mTc gamma imaging. The distribution of 51Cr and 99mTc-labeled, viable and nonviable, unreduced or SnCl2-reduced autologous lymphocytes was determined 2 hr following intravenous injection. Viable 99mTc-labeled lymphocytes localized primarily in the liver, lungs, and kidneys or remained circulating in the blood. These compartments accounted for 34-54% of the injected radioactivity. One to three percent of the injected dose was recovered from the spleen, thyroid, bladder, and stomach, and all remaining organs accounted for less than 1%. Reduced, nonviable cells showed increased localization in the lungs and liver (48%) compared to viable unreduced cells (15%). Chromium-51-labeled lymphocytes were distributed primarily to the liver, lungs, and spleen or remained circulating in the blood. Hepatic localization differed from that observed with viable, unreduced 99mTc-labeled lymphocytes (32 vs. 12%), but vascular compartmentalization was similar (18 vs. 15%). The distribution of pertechnetate and reduced 99mTc was different from that of 99mTc-labeled cells. The urine and blood accounted for 84% of the recovered radioactivity, and for 43-45% of the injected dose, indicating that the patterns we observed with 99mTc-labeled lymphocytes truly represented cell-associated radioactivity. Similarly, the distribution of Na251CrO4 differed from that of 51Cr-labeled cells. The kidneys and urine accounted for 26% of the injected dose, compared with 5% for 51Cr-labeled lymphocytes, and only trace amounts of radioactivity were found in the lungs and spleen. The distribution of 99mTc-labeled cells, as determined by scintigraphy 90 min after injection, correlated well with data obtained by postmortem counting, suggesting that 99mTc may be applicable as a lymphocyte label for diagnostic gamma-imaging procedures.