Although there is a large body of literature documenting the lethal cardiotoxic complications of tricyclic antidepressant (TCA) overdose, the absence of reliable predictive signs has led to a policy of admitting even trivial-appearing overdoses for inpatient observation. A study of 18 fatal cases revealed that with the exception of two that received clearly inadequate medical care, all fatal ingestions developed major signs of toxicity mandating admission within two hours of arrival at the hospital, and the mean time from arrival to death was only 5.43 hours. All patients who died of direct TCA toxicity did so within 24 hours of arrival. In addition, half the fatal cases presented with only trivial signs of poisoning, but deteriorated catastrophically within one hour. These data lead to an algorithm to guide admission of serious cases.