Background: Patients with cancer pain with initially adequate analgesia under oral sustained-release opioid medication may suffer from persisting pain exacerbations. Sometimes even fast help is needed and then optimally performed by intravenous application (IVA) of immediate-release (IR) opioids. This IVA, however, may only be performed by physicians in Germany. Objective: We wanted to find out if subcutaneous application of IR-opioids might be an adequate alternative to IVA in persisting pain exacerbations of patients with cancer pain because this could be performed by the nursing staff in Germany as well. Design: An open randomized controlled trial was used to compare intravenous versus subcutaneous morphine titration in persisting pain exacerbations in patients with cancer pain. Setting/subjects: Thirty-nine patients with cancer (21 intravenously, 18 subcutaneously) of the pain management department of the university hospital of Cologne, Germany were included into the study. Measurements: Calculated from preexisting analgesic medication boli of morphine were given every 5 minutes (intravenously) or 30 minutes (subcutaneously) up to adequate analgesia or intolerable side effects. Pain intensitiy, nausea, sedation, and some vital parameters were documented before the start, after each application and at the end of titration. Results: Thirty-five patients were pretreated with oral opioids, 4 patients with nonopioid analgesics. Six patients stopped titration because of intolerable side effects (sedation, vomiting). Thirty patients (77%) reported at least sufficient pain reduction, 3 patients were free of pain (intravenously). Mean pain intensity decreased on a visual analogue scale (VAS, 0-100) from 83 to 32 (intravenously) and from 68 to 42 (subcutaneously). Morphine doses ranged from 4 mg to 32 mg (intravenously; mean, 18.5 ± 9.2 mg) and from 10 mg to 200 mg (subcutaneously mean, 57.9 ± 59.6 mg). Mean time up to adequate analgesia was 53 (intravenously) 77 min (subcutaneously), respectively. There was no change in vital parameters but an increase of sedation in both groups. The adaptation of the continuous analgesic medication resulted in a stable and lasting pain relief after 4 days in both groups. Conclusions: Intravenous and subcutaneous-morphine titration are adequate to antagonize persisting pain exacerbations in cancer pain patients quickly and to adapt the continuous opioid analgesic medication.