To explore the causes of failure to activate the rapid response system (RRS). The organisation has a recognised incidence of staff failing to act when confronted with a deteriorating patient and leading to adverse outcomes. Design A multi-method study using the following: a point prevalence survey to determine the incidence of abnormal simple bedside observations and activation of the rapid response team by clinical staff; a prospective audit of all patients experiencing a cardiac arrest, unplanned intensive care unit admission or death over an 8-week period; structured interviews of staff to explore cognitive and sociocultural barriers to activating the RRS. Setting Southern Health is a comprehensive healthcare network with 570 adult in-patient beds across four metropolitan teaching hospitals in the south-eastern sector of Melbourne. Measurements Frequency of physiological instability and outcomes within the in-patient hospital population. Qualitative data from staff interviews were thematically coded. Results The incidence of physiological instability in the acute adult population was 4.04 . Nearly half of these patients (42 ) did not receive an appropriate clinical response from the staff, despite most (69.2 ) recognising their patient met physiological criteria for activating the RRS, and being `quite?, or `very? concerned about their patient (75.8 ). Structured interviews with 91 staff members identified predominantly sociocultural reasons for failure to activate the RRS. Conclusions Despite an organisational commitment to the RRS, clinical staff act on local cultural rules within the clinical environment that are usually not explicit. Better understanding of these informal rules may lead to more appropriate activation of the RRS.