This double-blind study compared mirtazapine's effects on alertness and sleep between parallel groups treated for 2 weeks according to a fixed regimen of 30 mg at bedtime (N = 69) and one that increased in dose from 15 to 30 mg at bedtime after the first week (N = 71). These patients with depression used an interactive telephone/computer system for daily alertness and sleep recordings on self-rating scales before and during treatment. Efficacy (17-item Hamilton Rating Scale for Depression [HAM-D], Clinical Global Impression Scale [CGI]) and safety assessments were made by participating psychiatrists. Both groups' alertness ratings were subnormal at baseline and even lower after the first dose. The ratings recovered after the second dose and increased progressively to levels 18% higher than those at baseline by the end of treatment. Patients receiving the fixed dose reported earlier sleep onset and longer duration. Similar mean changes in HAM-D scores (approximately -40%) and frequencies of CGI responders (>50%) occurred in both groups. The regimens were equally well tolerated. Somnolence, the most frequent side effect, was reported by only 10% of each group during the first week and by fewer patients during the second. Mirtazapine in fixed and ascending nocturnal dosing regimens was found to facilitate sleep, but it does not generally reduce daytime alertness. The fixed regimen seems preferable because of its greater effects on sleep.