With the view of investigating the metabolism of inter-alpha-inhibitor, a plasma serine-proteinase inhibitor, in an animal model of inflammatory syndrome, we isolated inter-alpha-inhibitor from pig plasma. A high yield was obtained (140 mg/liter) with a two-step procedure: anion-exchange chromatography followed by affinity chromatography on heparin-Sepharose. In contrast to bovine inter-alpha-inhibitor was highly similar to human inter-alpha-inhibitor: its heavy chains are homologous to the human H1 and H2 heavy chains, as shown by chromatographic and electrophoretic properties, cross-immunoreactivity and N-terminal sequencing. Pig may therefore represent a good animal model to study inter-alpha-inhibitor metabolism and elucidate its physiological role.