The recovery of the rat diaphragm from neuromuscular blockade was studied in order to separate the contributions of drug binding and tissue washout. The in vitro rat diaphragm preparation was perfused with a cholinesterase-free solution via the phrenic vein and stimulated electrically via the phrenic nerve. Muscle paralysis was induced by infusion of a depolarizing blocker succinylcholine or by the nondepolarizing blocker pancuronium. The time for recovery from 25-75% recovery averaged 1.0 +/- 0.1 min for pancuronium and 0.8 +/- 0.1 min for succinylcholine at the fast (1.9 ml/min) perfusion rate. This was prolonged to 2.0 +/- 0.3 min for pancuronium and 1.4 +/- 0.1 min for succinylcholine at the slower (0.76 ml/min) rate. More sensitive paired tests of recovery utilizing recovery time and rate demonstrated no drug difference in three comparisons and a 44% longer recovery time for pancuronium only at the lower perfusion rate. In general, recovery times were similar for both drugs. The rapid recovery from pancuronium blockade in this mammalian system as perfusion rate was increased suggests that recovery from this drug is not impaired by drug binding but is strongly dependent on organ perfusion.