An enzyme-linked immunosorbent assay (ELISA) to quantitate anti-lipid A antibodies in sera has been developed. The sensitivity of the ELISA was improved when the antigen (lipid A) was immobilized at pH 2.0, presumably by enhanced solid-phase adsorption of lipid A which is presumed to be aggregated at low pH. This was also verified by solid-phase immunoradiometry in which a four-fold improvement in the signal-to-noise ratio was observed when antigen coating was performed at pH 2.0 as compared to coating at pH 9.6. The enhanced sensitivity permitted the use of low concentrations of lipid A (10 μg/ml) for antigen coating of microtiter plates. The assay was able to clearly detect differences in IgG anti-lipid A levels between patients with chronic liver disease and normal controls.