A fatal toxicity index (deaths per million National Health Service prescriptions) was calculated for antidepressant drugs on sale during the years 1975-84 in England, Wales, and Scotland. The tricyclic drugs introduced before 1970 had a higher index than the mean for all the drugs studied (p less than 0.001). In this group the toxicity of amitriptyline, dibenzepin, desipramine, and dothiepin was significantly higher, while that of clomipramine, imipramine, iprindole, protriptyline, and trimipramine was lower. The monoamine oxidase inhibitors had intermediate toxicity, and the antidepressants introduced since 1973, considered as a group, had significantly lower toxicity than the mean (p less than 0.001). Of these newer drugs, maprotiline had a fatal toxicity index similar to that of the older tricyclic antidepressants, while the other newly introduced drugs had lower toxicity indices, with those for mianserin, nomifensine, trazodone, and viloxazine reaching significance. Provided that these drugs are equally effective clinically, serious consideration should be given to prescribing antidepressants with a lower fatal toxicity.