Objective: Reliadol® (Nycomed Denmark A/S) is a new modified-release morphine formulation undergoing clinical evaluation. It consists of a mixture of rapid- and modified-release microencapsulated granules of morphine. The study aims were to investigate the single-dose pharmacokinetics of morphine, its metabolites morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), after ingestion of Reliadol® (2 x 30 mg capsules) compared with Kapanolo (3 x 20 mg) [Glaxo Wellcome Australia Ltd] and an immediate-release morphine tablet (Morfin 'DAK', 30 mg; Nycomed Denmark A/S). Design and Setting: A three-way randomised, crossover study conducted in an inpatient drug studies' unit. Study Participants and Interventions: Twenty-four healthy volunteers took each formulation on three separate occasions after an overnight fast. Results: The dose-normalised areas under the plasma concentration versus time curve were equivalent for the three formulations for all three analytes. The time to achieve maximum plasma concentration (C(max)) was significantly shorter for Reliadol® (mean ± SD 4.0 ± 2.2 h for morphine; 4.9 ± 1.4 h for M6G; 6.0 ± 1.5 h for M3G) than for Kapanol® (7.9 ± 2.7 h for morphine; 9.3 ± 2.0 h for M6G; 9.7 ± 1.9 h for M3G), but significantly longer for the two modified-release formulations than for Morfin 'DAK' (0.83 ± 0.35 h for morphine; 1.6 ± 0.4 h for M6G; 1.4 ± 0.4 h for M3G). The C(max) of the three analytes was not different for the two modified-release formulations but was significantly lower for Morfin 'DAK'. The time over which the plasma concentration exceeded 75% of the C(max) was equivalent for Reliadol® (5.7 ± 2.6 h for morphine; 6.9 ± 2.0 h for M6G; 7.5 ± 2.0 h for M3G) and for Kapanolo (4.9 ± 2.2 h for morphine; 6.0 ± 1.8 h for M6G; 6.5 ± 2.1 h for M3G), but was significantly shorter for Morfin 'DAK' (0.76 ± 0.40 h for morphine; 1.4 ± 0.5 h for M6G; 1.4 ± 0.4 h for M3G). The time over which plasma concentration exceeded 50% of the C(max) and mean residence time were equivalent for Reliadol® and for Kapanol® but significantly shorter for Morfin 'DAK'. The most common adverse events were nausea and headache. Conclusions: Reliadol® is likely to be suitable for once-daily administration in patients with chronic pain because of its unique plasma concentration versus time profile resulting from the mixture of rapid- and modified-release morphine pellets.