We studied 88 healthy, ASA I patients (aged 20-45 yr), to determine if nitrous oxide affects thiopentone requirements for achieving 50% probability of no movement in response to verbal commands (C-P,C-50). Patients were allocated randomly to one of four nitrous oxide concentration groups (0%, 20%, 40% and 60%). Patients in each group were also allocated randomly to receive predetermined target plasma concentrations of thiopentone. Computer-controlled continuous infusion was used to maintain the target plasma thiopentone concentration, and this concentration was held constant for 6 min to ensure equilibration. The C-P,C-50 value of thiopentone in the absence of nitrous oxide was 14.8 mu g ml(-1). The reduction in C-P,C-50 by nitrous oxide was non-linear, and the interaction coefficient between nitrous oxide and thiopentone was significantly smaller than zero (P = 0.0274), indicating that nitrous oxide antagonized the ability of thiopentone to prevent response to verbal commands.