The circulating insulin–like peptide, NSILA–s (non–suppressible insulin-like activity soluble in acid–ethanol), was measured by a radioreceptor assay in which insulin is 1/300,000th as reactive and proinsulin is l/1000th as reactive. When plasma was filtered on Sephadex G–50 at pH 2.3, NSILA–s radioreceptor activity was recovered as a discrete peak. In 5 normal adults, plasma NSILA–s was 1200–2200 ng/ml. Elevated NSILA–s concentrations (2400–16,000 ng/ml) were detected in 5 of 7 hypoglycemic patients with nonislet cell tumors. Plasma NSILA–s was not elevated in 4 patients with similar tumors but without hypoglycemia, 3 with insulin–induced hypoglycemia, 2 with acromegaly and 3 with hypopituitarism. We suggest a possible role for NSILA–s in the etiology of the hypoglycemia associated with extrapancreatic tumors.