1. Glucose-infusion tests were performed on patients admitted for elective upper abdominal surgery 1 day before and 1 day after operation. In addition to insulin and proinsulin, a third immunoreactive insulin species of mol. wt. 20 000–30 000 was detected in plasma from two patients. The heterogeneity of plasma immunoreactive insulin (IRI) and the need to consider the effects of all forms, including proinsulin and the high-molecular-weight species, is emphasized.
2. During preoperative glucose infusions there was an increase in the percentage of the total plasma IRI present as high-molecular-weight forms (i.e. proinsulin plus the species of mol. wt. 20 000–30 000) from 3·9% to 10·8%. On the first postoperative morning all patients showed an increase in the amounts of the heavier IRI types, which accounted for 13·9% of the total plasma IRI.
3. The changes in insulin and proinsulin are consistent with the release from the pancreas of an insulin/proinsulin mixture of constant proportions, and the longer circulating half-life of proinsulin.
4. Increases in the amounts of high-molecular-weight IRI species after surgery may have a partial role in the development of insulin resistance but are probably not a major determinant of the insulin-resistant state.