Data presented show that lofepramine has lower acute toxicity for animals than other antidepressants tested. Review of 55 case reports of acute lofepramine overdose in man shows that hypotension was rare and convulsions did not occur, although in some cases large overdoses of several grams of drug had been taken. No deaths have been recorded due to overdose with lofepramine alone, and the fatal toxicity index for lofepramine (deaths per million prescriptions, England, Wales and Scotland, 1982-1986) is significantly lower than the mean of all antidepressants (P less than 0.001). It thus appears that the low toxicity of lofepramine in animal experiments applies also to man, and that this drug has a favourable safety profile when taken in acute overdose.