The biphasic depression of muscle contractions induced by succinylcholine (Sch) and decamethonium (C 10 ) in rat diaphragms at 32 °C was investigated. The type of depression induced by these muscle relaxants was dependent on their speed of administration and the experimental conditions. Contrary to present belief, endplate depolarization had a minor role in the mode of action of Sch and C 10 during the initial neuromuscular block (phase I); this initial phase was caused by a prejunctional failure similar for both drugs. The late depression of muscle contractions (phase II) had different causes depending on the drug used and could be present without the preceding phase I. Postjunctional desensitization may contribute to phase II block under C 10 but its role is insignificant, if any, under Sch. These results may be more relevant to the action of C 10 and Sch in man than observations made from muscles of frogs maintained at room temperature. However, until these observations are tested in human muscles in situ we cannot be sure of their applicability to the clinical situation.