In this double-blind study alpidem, a new imidazopyridine anxiolytic drug, was compared with placebo to assess its efficacy and safety in severely anxious patients at the fixed dose of 150 mg/day (50 mg t.i.d.) for 3 weeks. Fifty-nine patients with a score of at least 18 on the Hamilton Rating Scale for Anxiety (HRSA) entered the trial after a 3- to 7-day placebo run-in period. Symptom improvement was evaluated with the HRSA, the State and Trait Anxiety Inventory (STAI-1 and STAI-2), a Visual Analogue Scale (VAS) and the Clinical Global Impression (CGI). Alpidem was more effective than placebo in improving mean HRSA (total score and factorial scores for somatic and psychic anxiety), STAI-1 and STAI-2 and VAS scores. The efficacy index of the CGI was better for alpidem than for placebo. Side effects were negligible in both groups. Alpidem appears to be a new interesting anxiolytic drug devoid of significant sedative effects on mental functions.