Fourteen out-patients with major depressive disorder completed a double-blind, randomized, parallel group study using trazodone (n = 6), amitriptyline (n = 5) and matching placebo (n = 3). The average daily doses used were 223 mg and 95.3 mg for trazodone and amitriptyline, respectively, over the 28-day treatment period. Cardiovascular function was monitored with high speed ECG and by determining systolic time intervals. No significant effects of either drug on supine or standing blood pressure were demonstrated. Trazodone increased QTc on Day 1 only, and reduced heart rate and increased the PR interval on Day 15; these effects had disappeared by Day 29. Amitriptyline markedly increased heart rate, PR interval and QTc, and reduced T wave amplitude on Days 15 and 29. Trazodone had no consistent effect on systolic time intervals except to increase the LVET index, whereas amitriptyline increased both PEP index and PEP/LVET ratio on Days 15 and 29. It is concluded that amitriptyline had a much more marked effect on cardiac function than did trazodone.