It is fairly widespread clinical practice to administer large doses of corticosteroids to patients in cases of shock; doses of hydrocortisone as high as 50 mg · kg−1given intravenously have been proposed and used. Hydrocortisone, when administered in this way during surgery, has been implicated in interactions with neuromuscular blocking agents. In order to determine the type and mechanism of this interaction, the authors undertook further investigation. The effects of hydrocortisone were studied in two ways. Firstly, a constant 50% depression of the indirectly elicited twitch tension of the tibialis–anterior muscle was established in cats, using a constant intravenous infusion of either pancuronium (1.0 · 0.2 μg · kg−1· min−1) or succinylcholine (3.6 · 0.8 μg · kg−1· min−1). The effects of intravenous hydrocortisone then were studied on this block. Secondly, cats chronically were treated with 2 mg · kg−1of intramuscular hydrocortisone three times a week for 1 month, and then dose-response curves were constructed for pancuronium or succinylcholine. Acute administration of intravenous hydrocortisone (1–15 mg · kg−1) alone had no affect on the twitch tension of either the tibialis–anterior or soleus muscles, however, the corticosteroid (7 and 15 mg · kg−1) did significantly (P< 0.05) enhance the 50% depression of the indirectly elicited twitch tension of the tibialis–anterior muscle produced by the constant intravenous infusion of pancuronium. The soleus muscle was affected similarly (n = 6). Under the same conditions, with a constant infusion of succinylcholine, hydrocortisone had no effect on the blockade of the tibialis–anterior muscle or the soleus muscle (n = 6). The chronic treatment of male cats with hydrocortisone had no effect on the sensitivity to pancuronium (n = 6) of both the tibialis–anterior and soleus muscles. However, this treatment did produce a significant (P< 0.05) change in sensitivity to succinylcholine (n = 6) on the tibialis–anterior muscle but not on the soleus muscle. Two of the 12 cats chronically treated with hydrocortisone exhibited histologic evidence of myopathy. It is concluded that hydrocortisone can enhance the neuromuscular blocking effect of pancuronium and that chronic hydrocortisone treatment can modify the response to succinylcholine. In either case, monitoring of neuromuscular transmission during anesthesia is suggested when a patient is receiving either high-dose acute or chronic hydrocortisone therapy.