Morphine and tubocurarine may release histamine by direct mast cell degranulation which may result in systemic effects such as cutaneous flushing, local wheal and flare formation and hypotension. This randomised, double‐blind study examined whether pre‐operative combined oral terfenadine (60 mg) and ranitidine (150 mg) attenuates the reduction in blood pressure and cutaneous flushing after the administration of tubocurarine and morphine in 60 patients undergoing elective gynaecological surgery. In addition, investigation was made of whether tubocurarine and morphine cause a significant decrease in gastric pH in comparison to the nonhistamine‐releasing agents fentanyl and vecuronium. Patients were randomly assigned to one of three groups receiving either pre‐operative terfenadine and ranitidine and intra‐operative tubocurarine and morphine (group A); pre‐operative placebo and intra‐operative tubocurarine and morphine (group B); pre‐operative placebo and intra‐operative fentanyl and vecuronium (group C). Compared to group B, group A had less hypotension and tachycardia but no significant decrease in cutaneous flushing immediately following morphine and tubocurarine (p > 0.05). There were no significant differences in haemodynamic changes between the groups A and C. In those patients not pretreated with terfenadine and ranitidine (groups B and C), gastric pH decreased between 5 and 10 min following bolus administration of morphine and tubocurarine (group B), whereas patients receiving fentanyl and vecuronium (group C) had an increase in gastric pH. This suggests that histamine release following administration of morphine and tubocurarine is sufficient to increase gastric acidity. These results indicate that for routine prophylaxis of high risk patients and for patients who have had a previous anaesthetic anaphylactoid reaction, oral premedication with the newer H₁ and H₂ receptor antagonists may be useful. Furthermore, systemic liberation of histamine may cause a significant decrease in gastric pH with the attendant risk of aspiration pneumonitis.