We have investigated the dose-effect relationship of neostigmine in antagonizing vecuronium-induced neuromuscular block with and without magnesium sulphate (MgSO4) pretreatment. Neuromuscular block was assessed by electromyography with train-of-four (TOF) stimulation. First, we determined neostigmine-induced recovery in patients pretreated with MgSO4 (group A) or saline (group B) (n = 12 each). The height of T1, 5 min after neostigmine, was 43 (7)% in group A and 65 (6)% in group B (P < 0.01). Respective values after 10 min were 59 (7)% and 83 (5)% (P < 0.01). TOF ratio, 5 min after neostigmine, was 29 (6)% in group A and 29 (5)% in group B. Respective values after 10 min were 38 (11)% and 51 (7)% (P < 0.01). To gain insight into the mechanisms leading to delayed recovery after MgSO4, we calculated assisted recovery, defined as neostigmine-induced recovery minus mean spontaneous recovery. Spontaneous recovery was assessed in another 24 patients. Patients in group C received MgSO4/vecuronium and patients in group D vecuronium only (n = 12 each). Five minutes after neostigmine, assisted recovery was 22 (7)% in the MgSO4 pretreated patients and 28 (6)% in controls (P < 0.05). Ten minutes after neostigmine, values were 24 (7)% and 22 (6)%. Maximum assisted recovery was not influenced by MgSO4 pretreatment (27 (6)% in group A and 32 (6)% in group B) and time to maximum effect was comparable between groups: 6 (4-10) min and 7 (5-8) min, respectively. We conclude that neostigmine-induced recovery was attenuated in patients treated with MgSO4. This was mainly a result of slower spontaneous recovery and not decreased response to neostigmine.