Esmolol, a new cardioselective beta adrenergic blocker inhibits plasmacholinesterase activity in vitro. The concentration of esmolol hydrochloride that inhibits by 50 per cent the hydrolysis of 50.0 mumol.L-1 benzoylcholine hydrochloride by 1:200 diluted, heparinized pooled plasma of six healthy volunteers at 37 degrees C and 240 nm, determined by the ultraviolet spectrophotometric method of Kalow, was 50 mumol.L-1. Esmolol's primary metabolite, 3-[4-(2-hydroxy-3-(isopropylamino)propoxy)-phenyl]propionic acid, had an I50 = 190 mumol.L-1. The benzoylcholine hydrolysis rates in the plasma of ten patients who received an esmolol infusion of 500 micrograms.kg-1.min-1 for 4 minutes were 58.6 +/- 6.2 mumol.hr-1.ml-1 (mean +/- SE) before and 55.1 +/- 6.6 mumol.hr-1.ml-1 after the infusion. The benzoylcholine hydrolysis rates in the plasma of ten patients who received an esmolol infusion of 500 micrograms.kg-1.min-1 for two minutes and 200 micrograms.kg-1.min-1 for an additional two minutes were 70.2 +/- 8.9 mumol.hr-1.ml-1 before and 69.1 +/- 9.5 mumol.hr-1.ml-1 after the infusion. The pre- and post-infusion plasmacholinesterase activities were not significantly different. Since plasmacholinesterase is responsible for the hydrolysis of succinylcholine and that of the ester-type local anaesthetics this lack of in vivo interaction of esmolol with the hydrolysis of these drugs should be further confirmed by experiments with these combinations in man.