We studied alteration in macrophage activity during experimental septic shock and the effect of the protease inhibitor Trasylol® on these alterations. Studies were carried out on three groups of 6 rabbits of each. One group (A) served as a control and in the other two groups (B, C) septic shock was induced using the cecal ligation technique. Group B received i.v. Trasylol prior to and following cecal ligation. The clearance and reticuloendothelial system (R.E.S.) distribution of 125I labelled polyvinyl pyr-rolidone (PVP) was used to study macrophage function. PVP was injected into all animals 18 h prior to cecal ligation. for 48 h following the operation, PVP blood levels were repeatedly measured and clearance calculated. The animals were then sacrificed, and total radioactivity of the various organs was measured. In the early stages after cecal ligation a significantly higher PVP clearance rate was noted in groups B and C (P < 0.01); In the later stages of the experiment, however, group C demonstrated the slowest clearance rate with intermediate values in group B. The highest PVP concentrations were found in the liver and spleen. A significantly higher PVP concentration was noted in the spleen of the animals in group A and B as compared to group C (P < 0.01) while the difference between group A and B was not significant. Our results indicate that septic shock reduces macrophage function as measured by the changes in PVP clearance and distribution. Injections of Trasylol seem to ameliorate these changes. The model of 125I PVP clearance seems to offer a convenient, valid and informative model for measurement of macrophage activity in pathological conditions.