Effects of single oral doses of the beta-blocking drugs propranolol (40 mg) and metipranolol (Disorat, Boehringer, Mannheim, FRG, 5 and 20 mg), in comparison with placebo, on mental performance and psychophysiological measures were investigated in a double-blind crossover study comprising 12 healthy volunteers. Effects were evaluated using a battery of highly reliable and sensitive computerized indices of mental performance and a comprehensive range of psychophysiological measures. Propranolol and metipranolol had no effects on mental performance, in contrast to findings in a previous study for bunitrolol (Stresson, Boehringer, Ingelheim, FRG). There were marked effects on some autonomic functions; dose-dependent for heart rate and heart rate response, and dose-independent for blood pressure and finger tremor. In the previous study bunitrolol had no effect on tremor and blood pressure and a less marked effect on heart rate. The lack of psychotropic effects for metipranolol and propranolol as compared to bunitrolol cannot be predicted from pharmacokinetic properties or peripheral effects of the three drugs, arguing for the need for systematic screening using psychometric and psychophysiological methods of current and new beta-blocking drugs. A comparison between the effect of propranolol given in a single oral dose and findings in a previous study with repeated administration suggested that the differences in effect profile between acute and chronic administration of the drug are small.