Uptake of rat and human cc,-macroglobulin-trypsin complexes was measured in rat hepatocytes, rat and human adipocytes and human fibroblasts. Uptake and degradation of 1251-labelled rat complex were about one-third of that of the human complex in the various isolated cell types. In rat hepatocytes, the apparent K,,, for cell association of the rat complex was about 16 nM as compared to about 6 nM for the human complex. The V,,, values were similar, about 1 x lo4 molecules cell-l min-1. Thus, rat cr,-macroglobulin (an acute-phase protein) complexed with trypsin follows the same pathways of uptake as the human homologue, although with a somewhat lower affinity for the uptake system.