Our purpose is to study the analytical and clinical toxicology of acute drug overdose, which usually follows suicide attempts, in order to improve clinical laboratory diagnosis and support, and increase knowledge of plasma drug and drug metabolite levels following drug overdose. This includes development of procedures which are suitable for around the clock emergency use, as well as the development of more sensitive, specific procedures to determine the concentrations of patent drug and metabolite following overdose; the latter data also will be used for clinical correlation studies. Previously we described a procedure for the emergency analysis of the drugs most commonly involved in overdose. We developed and tested on clinical specimens a computer program for processing the analytical data which reduces the need for specialized knowledge by the technologist. We have also evaluated the possible application of an automated G.C.-M.S. to "routine" emergency toxicology. We also published studies of the clinical correlation of plasma levels of chlordiazepoxide, methyprylon and methaqualone and tricyclic antidepressants. We have noted that parent drug to metabolite ratios are particularly useful in evaluating acuteness of overdose. Our emergency procedures which rely on UV spectrophotometry are particularly suited to emergency toxicology, and are used for case finding. More sensitive and specific procedures including gas chromatography with selective (nitrogen) detectors, and HPLC are being developed to determine accurate concentrations. We are completing clinical correlation studies of chlordiazepoxide (and its two active metabolites), and diazepam (and nordiazepam). During the coming year we also hope to study phenothiazine overdose. We also plan to study the application of HPLC to the acute rapid diagnosis of tricyclic antidepressant overdose, as well as to general, rapid overdose screening. The methods developed, and knowledge obtained studying overdose, should also be of value to those involved in clinical pharmacologic studies of therapeutic levels.