We describe in this paper a novel approach for the detection of neutralizing antibodies (NAbs) and the assessment of their impact on drug exposure. This approach is based on an in-vitro cell-based bioassay utilizing receptor tyrosine phosphorylation as a cellular endpoint and comprises of two assay formats: a quantitative assay for measurement of bioactive drug concentrations in a serum sample, and a neutralizing antibody detection assay. The bioassay utilizes PC-3 cells that respond to treatment with hepatocyte growth factor (HGF) with phosphorylation of tyrosine residues on c-Met, the receptor for HGF. The drug, a fully human monoclonal antibody to human HGF, inhibits the HGF-induced response in a dose-dependent manner that can be used for quantitative determination of circulating drug levels in serum samples. The approach described here consists of testing a sample with and without an exogenously added concentration of drug. Testing the sample for its inherent bioactivity allows a determination of the circulating levels of bioactive drug. Testing the same sample with an exogenously added concentration of drug and an assessment of its analytical recovery allows a determination of NAb presence. Neutralizing antibodies, if present, are expected to impair the recovery of the exogenously added concentration of drug. This approach provides utility in gaining clinically relevant information when NAb detection is hindered by high levels of circulating drug levels using conventional NAb assay formats. Validation of this method is described in detail along with discussions on the utility of this approach.