The high concentrations of amitriptyline found in blood at autopsy, indicating a large amount of ingested drug, is often contradictory to the prescription available. Using dogs as the animal model it was found that there was a large variance between the dose given and its plasma amitriptyline concentration during the acute phase of absorption. Factors that were found to be important were the amitriptyline to nortriptyline (as metabolite) ratio, the nature of the specimen, and the collection site. The calculation of the dose from an acute ingestion of amitriptyline resulting in death cannot be accurately determined from a single specimen collected at autopsy.