Islets of Langerhans from NMRI-mice were kept for one week in tissue culture in medium supplemented with human serum obtained from either normal healthy subjects or newly diagnosed juvenile diabetic patients before insulin treatment. Islets cultured in diabetic serum released more insulin than islets cultured in normal serum, whether tissue culture medium 199 with 5.5-8.3 mmol/l glucose and 10% serum, or culture medium RPMI 1640 with 11 mmol/l glucose and 0.5% serum were used. Islets kept for one week in culture with diabetic serum did not show any decrease in DNA content or glucose induced insulin secretion and biosynthesis. It is concluded that serum from newly diagnosed insulin-dependent diabetic patients stimulates insulin release from isolated mouse islets kept in tissue culture. The underlying mechanism is unknown.