Total plasma immunoreactive insulin (IRI) and percentage “big” insulin (proinsulinlike material) were measured in a patient with an inoperable islet cell carcinoma who did not improve clinically after streptozotocin administration. Prior to the streptozotocin, the total IRI rose with administration of tolbutamide, and the percentage of “big” insulin remained constant. After intravenous glucose there was little change in plasma IRI, but a substantial rise in the percentage of “big” insulin occurred. The administration of streptozotocin was acutely associated with hypoglycemia, a slight increase in total IRI, and no change in the percentage “big” insulin. With chronic administration and extension of the disease, the total IRI and percentage “big” insulin rose progressively. It is concluded that the percentage “big” insulin rises as loss of tumor differentiation occurs and that changes in the percentage of “big” insulin after streptozotocin may give an early indication of likely response to streptozotocin.