Hypotension is an uncommon complication of procedures involving extracorporeal circulation, including plasmapheresis. From November 1993 to March 1999, we treated 139 patients who underwent a total of 1,137 sessions of double filtration plasmapheresis (DFP). Hypotension was defined as a systolic blood pressure (BP) < 80 mm Hg or any decrease of systolic BP with systemic reactions. A total of 17 (1.5%) episodes of hypotension were documented in 15 patients during the study period. Hypotensive episodes occurred in 2.3% of patients with inflammatory neuropathy, 1.2% of patients with myasthenia gravis, and 1.2% of patients with all other medical diseases. Involvement of the autonomic nerve system (ANS) and a low baseline BP were associated with the occurrence of hypotension. Eight (47%) of 17 episodes were symptomatic and 2 were complicated with seizure. Patients with symptomatic hypotension had a higher level of systolic BP prior to DFP and a larger drop of systolic BP and pulse rate during hypotensive attacks compared to asymptomatic patients. Most hypotensive episodes were resolved briefly after intravenous infusion of saline within 30 min. Eight (47%) of the hypotensive episodes occurred during the first session of DFP treatment. Twelve (71%) of 17 episodes occurred during the last half period of treatment; 6 of them were noted during the terminating stage of DFP. In conclusion, in this series plasmapheresis-related hypotension occurred in 1.5% of DFP sessions and had a higher prevalence in patients with ANS instability and low BP. Extra caution in monitoring BP during DFP therapy is warranted in these vulnerable patients, especially during the termination phase of the first DFP session.