1 Interactions between codeine and promethazine have been studied in male and female volunteers, measuring ventilation, end tidal PCO2, ventilatory response to CO2, pulse and blood pressure. 2 The effects of codeine on the above measurements have been compared in subjects who habitually smoke cigarettes and non smoking subjects. 3 Codeine displaced the ventilatory response to CO2 to the right and increased end tidal PCO2 in female subjects but not in males. 4 Promethazine plus codeine displaced the ventilatory response to CO2 to the right in male subjects but tended to reduce the response to codeine in females. 5 The slope of the ventilatory response to CO2 was significantly steeper in smokers and codeine caused significant reductions in slope in these subjects.