Nonsuppressible insulin-like activity soluble in acid ethanol (NSILA-s) is a well-characterized peptide derived from human serum which has previously been shown to have insulin-like bioactivity and react with both insulin and NSILA-s receptor sites in liver plasma membranes. In the present study we find that NSILA-s is also a potent competitive inhibitor of the insulin-degrading system of the liver plasma membrane. The most purified NSILA-s preparation tested was 20-fold more potent than insulin itself, and significant inhibition of insulin degradation occurred at concentrations of NSILA-s similar to those found in plasma.