During surgery and anesthesia, various physiologic and pharmacologic changes occur which may alter the pharmacokinetics and pharmacodynamics of pancuronium and d-turbocurarine and their antagonists, neostigmine and pyridostigmine. In the first section, we will develop a conceptual model and experimental paradigm for study of the clinical pharmacokinetics and dynamics of neuromuscular blocking and reversal drugs. In the second section, we will determine the pharmacokinetics and pharmacodynamics of neostigmine and pyridostigmine in normal anesthetized patients and in those with renal failure and with different anesthetic techniques. In the fourth section, we will attempt to develop a biochemical analytical technique which will measure the concentration of pancuronium and its metabolites in body fluids. Our present fluorimetric assay does not distinguish between unchanged pancuronium and its metabolites. With this new technique, we will not only determine the pharmacokinetics and dynamics, but the rate and extent to which pancuronium is metabolized in man.