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We hypothesized the general anesthetic thiopental effect depending on NO-related mechanisms, consequently counteracted by stable gastric pentadecapeptide BPC 157. (i) To determine the general anesthetic effect of thiopental and possible counteraction depending on BPC 157 administration, all rats received intraperitoneally thiopental (20, 30, 40 mg/kg) while medication (BPC 157 (10 μg/kg, 10 ng/kg, 10 pg/kg) was given intraperitoneally at 5 min before thiopental. (ii) To determine NO-related mechanisms, all rats received intraperitoneally thiopental 40 mg/kg while BPC 157 (10 μg/kg), L- NAME (10 mg/kg), L-arginine (30 mg/kg) were applied alone and/or combined. BPC 157 was given at 25 min before thiopental while L-NAME, L- arginine, alone and/or combined, were applied at 20 min before thiopental. (i) BPC 157 (10 ng/kg and 10 μg/kg), caused significant antagonism of general anesthesia produced by thiopental with a parallel shift of the dose- response curve to the right. (ii) L-NAME. Thiopental-induced anesthesia duration was tripled. L-arginine. Active only given with L- NAME or BPC 157: habitual thiopental anesthesia time not influenced ; potentiating effects of L-NAME lessened, not abolished ; shortening effect of BPC 157: abolished. BPC 157 and L- NAME. Potentiating effects of L-NAME was abolished. L-NAME and L-arginine and BPC 157. L- NAME+L-arginine+BPC 157 rats exhibited values close to those in BPC 157 rats. Thiopental general anaesthesia is simultaneously manipulated in both ways with NO-system activity modulation, L-NAME (prolongation) and BPC 157 (shortening/counteraction). BPC 157 and L- arginine might serve two NO-system pathways, more or less active, alternatively activated.