Pharmacological studies of premazepam in animals predicted antianxiety activity without sedation and, in combination with diazepam, a reduction in the sedative effects of the latter. The effects of single doses of premazepam (25 and 50 mg), diazepam (10 mg), premazepam (25 mg) plus diazepam (10 mg), and a placebo on subjective feelings, psychological tests and the EEG were studied in a double-blind cross-over study in 10 healthy subjects. In a repeated dose study in eight subjects, the effects on subjective feelings, psychological tests and the EEG of premazepam (5 and 10 mg twice-daily), diazepam (5mg twice-daily) and a placebo were compared. Premazepam had a different EEG profile from diazepam, producing more slow and less fast wave activity. In the single dose study its effects were similar to diazepam for sedative action and most of the psychological tests, with a tendency towards greater psychomotor impairment. In the repeated dose study, however, premazepam caused less sedation and also tended to produce less psychomotor impairment. The combination dose of premazepam (25 mg) plus diazepam (10 mg) in the single dose study indicated an additive effect rather than an antagonistic one.