Radioenzymatic assays are sensitive analytic tools that use an enzyme to quantify a substrate for that enzyme. Purified histamine N-methyltransferase has been used as the basis for an assay for histamine. The sensitivity of the procedure is < 10 fmol. The specificity of the assay is increased when the transferase reaction is carried out at 0-3-degrees-C. Data documenting the precision of the assay, the stability of histamine in human plasma, and the gastric secretory rate of histamine are presented along with a chronologic description of the development of the technique.