A 28-day, double-blind study involving 56 outpatients ws initiated to compare the anxiolytic efficacy and safety of ketazolam once a day at bedtime (HS) with diazepam given three times a day (TID) and placebo HS or TID. Ketazolam HS was at least equivalent, and in some respects superior, to diazepam TID with fewer, less severe side effects. The superiority of ketazolam over placebo was demonstrated on all five instruments used to evaluate efficacy, three rated by the physician and two by the patient. The efficacy of ketazolam was significant at all three follow-up evaluations, whereas significant results for diazepam were achieved mainly at weeks 1 and 2, with little seen at week f. Fewer side effects were reported with ketazolam than with diazepam and were mild in 84% of cases. One-third of the side effects reportd in the diazepam group were moderate or severe. The optimum daily dose was 54.5 mg ketazolam or 24.7 mg diazepam.