Our research has as its ultimate clinical goal to evaluate mechanisms whereby an important cardiovascular drug, propranolol, may have its disposition and activity altered by a second drug. By knowing situations where propranolol activity might be augmented or decreased, a physician may realize that an altered dosing schedule for propranolol is required when his patient is also receiving a drug which is shown to markedly affect propranolol. We are also demonstrating some aspects of first pass metabolism. This phenomenon is not well described in terms of drug interactions. We have a working hypothesis for how hepatic metabolism and binding lead to the differences which have been observed between various routes of administration or following drug interactions. Further tests are underway which may more fully validate this hypothesis. Such information should be useful to a general understanding of the pharmacokinetics of first pass metabolism. Finally, we have developed a sensitive reproducible method for the quantitative assay of propranolol and its metabolites in urine. It may ultimately be applied to clinical studies of drug disposition where the use of radiolabeled drug might otherwise be required, yet undesirable.