The plasma concentration-time profile and haemodynamic effects of metoprolol after the administration of metoprolol CR (a new multiple-unit controlled-release formulation) and metoprolol SR (a traditional slow-release formulation) once daily, were investigated in 12 healthy men. Data were collected over one 24-h dose interval at steady state after five days of treatment. The study was a randomized, three-way, cross-over comparison of metoprolol CR, 100 mg, metoprolol SR, 100 mg, and placebo. The reduction in exercise heart rate in relation to placebo treatment was used as a measure of beta 1-blockade. The metoprolol plasma concentration-time profile during treatment with metoprolol CR was smooth and uniform, showing a more controlled release profile than that obtained with metoprolol SR. This was demonstrated by the significantly longer time period during which the plasma concentration exceeded 75% of the maximum concentration (T75), for metoprolol CR compared with metoprolol SR (p less than 0.05). The percentage peak-trough fluctuation in plasma metoprolol concentration was significantly smaller for metoprolol CR than for metoprolol SR (p less than 0.001). These pharmacokinetic differences between metoprolol CR and metoprolol SR produced a different duration of clinically relevant beta 1-blockade, defined as a reduction in exercise heart rate of greater than 10%. By this definition metoprolol CR was still effective in seven subjects and metoprolol SR in two subjects 24 h after dosing. The percentage peak-trough fluctuation in exercise heart rate over the dose interval was significantly smaller for metoprolol CR than for metoprolol SR (p less than 0.001), thus demonstrating a more even beta 1-blockade with metoprolol CR.