This article describes the biochemical and chemical-toxicological investigations into the properties of the pericardial fluid designed to improve the effectiveness of forensic medical examination of the cases of fatal drug poisoning. The objectives of the study were the detection and determination of the type of narcotic substances in the pericardial fluid, evaluation of the quantitative changes in enzyme activities (AST, ALT and CPK) in the pericardial fluid, and the development of the criteria for the forensic medical diagnostics of fatal drug poisoning. The materials used in the study were the pericardial fluid and blood taken during forensic medical examination of 247 corpses of men (87.04%) and women (12.96%) at the age from 13 to 35 years who died from different causes. They were divided into two groups. The study group was comprised of 142 subjects who died from drug poisoning, the control group consisted of 105 subjects who died from other causes. The methods used to study the pericardial fluid included gas-liquid chromatography to detect the presence and the type of the poisonous drugs, as well as biochemical and colorimetric methods to determine the amount of enzymes AST, ALT, and CPK. The study revealed no traces of drugs or their metabolites in the pericardial fluid from the 105 control corpses. Positive results of the forensic drug tests were obtained in all the 142 cases of the study group. The changes in the parameters and the biochemical composition of pericardial fluid and blood in fatal drug poisoning were reliably established including the alteration of the enzyme levels, such as AST, ALT, and CPK. In the control group, the quantitative parameters of the enzyme activities did not exceed the normal values whereas in the study group a significant increase of AST, ALT, and CPK levels in the pericardial fluid and blood in comparison with the normal values was documented. Conclusion: the results obtained in the studies of both groups provide a basis on which to propose the reliable criteria for forensic medical diagnostics of fatal drug poisoning taking into consideration the changes in the chemical, toxicological, and biochemical parameters of the pericardial fluid.