A previously healthy 33-year-old woman received neuromuscular blocking agents during treatment of severe adult respiratory distress syndrome secondary to pneumococcal pneumonia and septic shock. Atracurium infusion rates were progressively increased, preceded by repeated loading doses up to a maximum of 3.57 mg/kg/hour, but produced inadequate neuromuscular blockade as assessed by clinical and ventilatory parameters as well as train-of-four (TOF) monitoring. Atracurium was discontinued and vecuronium infusions of 2.3 mg/kg/hour finally produced adequate paralysis for 7 days. Increasing vecuronium requirements then prompted discontinuation of neuromuscular blockade. Atracurium was reinstituted 2 days later because of worsening pulmonary function. Infusion rates of 3.04 mg/kg/hour were again required, together with high-dose midazolam and fentanyl, to achieve adequate oxygenation with acceptable airway pressures; however, TOF monitoring showed an unacceptable level of paralysis. Cross-resistance among chemically dissimilar neuromuscular blocking agents poses a difficult patient management problem and supports a pharmacodynamic basis of resistance to these agents.