Murine liver-derived inhibitory protein (LIP) capable of inhibiting human lymphocyte proliferation was highly purified from liver extract. Its molecular weight determined by gel filtration and SDS-PAGE was 105,000 and 38,400 respectively. LIP moved electrophoretically at the gamma-globulin region. Its activity in inhibiting lymphocyte proliferation was temperature-stable up to 60 degrees C, and pH-stable between 4 and 11. It was not cytotoxic to lymphocytes as shown in 51Cr-release experiments. The purified LIP possessed arginase activity.