A photoreactive derivative of procaine, p-azidobenzoyldiethylaminoethanol hydrochloride, has been synthesized and used as a site-directed probe to label hepatocyte plasma membranes. The procaine derivative was shown to have membrane binding and Ca2+ displacement characteristics quite similar to that of procaine. Photolysis of the derivative in the presence of hepatocyte plasma membranes resulted in the covalent incorporation of the probe into both the protein and lipid fractions. Analysis of the labeled membranes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that one membrane protein was significantly labeled with a molecular weight of 21 400 in addition to membrane lipids. Both binding and labeling could be inhibited in the presence of an excess of procaine. The labeled membrane components may be involved in the binding of Ca2+ to the membrane system.