The presence of drugs of abuse in saliva of human subjects after drug administration was studied to determine the feasibility of drug testing with saliva as the biological specimen. Healthy subjects with a history of chemical substance abuse volunteered for these studies. Informed consent was obtained and all procedures were approved by the hospital Institutional Review Board. Following the administration of cocaine, marijuana or opiates, saliva and blood samples were collected periodically. Behavioral and physiological measures were made concurrently with collection of biological fluids. Samples were analyzed by radioimmunoassay and gas chromatography/mass spectrometry. Significant correlation's of blood levels with saliva levels were found for cocaine and opiates. These studies provide the scientific basis for development of new non-invasive saliva tests for drugs of abuse.