Morphine and other potent opioids are frequently used in palliative care and pain management. When sustained-release (SR) opioids do not provide adequate background analgesia, additional immediate-release (IR) opioid (e.g. short-acting morphine) may be required to alleviate breakthrough or episodic pain. Despite the frequent use of IR morphine on top of SR opioids, little is known about the effects of such treatment on patients' everyday cognitive functioning. This study therefore used a double-blind, placebo-controlled, cross-over design to assess cognitive functioning in 14 patients receiving palliative care. All patients were taking SR opioid preparations and required <or=2 doses of IR morphine/day. Performance on cognitive measures (as well as subjective measures of pain and mood) after a dose of IR morphine was compared with placebo. Patients experienced significantly more pain-reduction following IR morphine (P=0.03), while other measures of subjective drug effects (e.g. sedation) were largely unaffected. Patients displayed anterograde memory impairment after IR morphine relative to placebo (P=0.003). Intriguingly, patients also had significant 'retrograde' memory impairment: delayed recall of verbal information presented before IR morphine also declined (P=0.024). In addition, IR morphine reduced performance on a complex tracking task (Reitan's trails B; P=0.03) whilst enhancing it on a simpler tracking task (Reitan's trails A; P=0.03). In conclusion, this study suggests that IR morphine, when taken on top of a SR opioid, produces transient anterograde and retrograde memory impairments and a decrement in two-target tracking. These impairments may impact negatively on patients' everyday functioning.