To examine the clinical spectrum of complications in pulmonary system and changes of some parameters of humoral and cell mediated immunity related to heroin overdose. The study includes 16 patients who are long-term heroin abusers with acute heroin and mixed with other psychoactive drugs intoxications with an average age of 21,5 ± 5.04 years (12 men and 4 woman). All patients were hospitalized in the Clinic of Toxicology, MHATEM “N.I.Pirogov”, Sofia. We have used clinical, clinico-laboratory, immunological, chimicotoxicological, instrumental methods. In severe intoxications with heroin and other psychoactive drugs, we observed pulmonary system complications, i.e. pneumonia, aspiration of gastric contents, noncardiogenic pulmonary edema (NCPE) and acute respiratory distress syndrome (ARDS.). Of the 16 patients in our study, 3 patients died due to complications. Some changes in the immune reactivity observed in the study were (1) statistically significant lower mean levels of IgG and (2) tendency to lower mean levels of IgA, IgM and complement components - C3 in the studied patients in comparison with the values in healthy people. The changes were more demonstrative in the group with pulmonary complications compared to the group without pulmonary complications. We observed that the CD4 lymphocytes were significantly less in the studied patients; in addition, a lower level of CD56-bearing lymphocytes (natural killer /NK/ cells) was observed in comparison to healthy controls. The results show that the mixture of acute heroin with other psychoactive drugs leads to complications in the pulmonary system and changes of some parameters of cell-mediated and humoral immunity.