We describe a method to improve the sensitivity of surface plasmon resonance (SPR) immunoassays using a horseradish peroxidase (HRP)-catalyzed precipitation reaction. The precipitation reaction catalyzed by HRP bound to the SPR biosensor surface via a sandwich immunoassay induced a shift in the SPR angle. Human interferon (IFN)-gamma at concentrations ranging from 0.01 to 100 ng/ml was detectable by this method. We also show that this biocatalytic signal amplification method can be applied to SPR imaging (SPRI), in an immunoassay of multiple proteins on a protein microarray format.