An ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS) method has been developed for the methamphetamine, morphine and O6-acetylmorphine in saliva. The sample was extracted and the protein was precipitated with acetonitrile. The matrix-matched standard solutions were used to prepare the curve of quantitative analysis. The drugs were separated on a BEH HILIC UPLC column. The mass spectrometric acquisition was carried out by means of electrospray ionization in positive mode (ESI+ ) with multiple reaction monitoring (MRM) method. The isotope internal standards were used to check the drugs. The average recoveries at four levels of 10, 20, 50 and 100 microg/L ranged from (68.7 +/- 6.5)% to (110.8 +/- 4.6)%. The intraday precisions were lower than 16.5% and interday precisions were lower than 16.3%. The detection limits (LOD, S/N > 3) and the quantification limits (LOQ, S/N > 10) of the three drugs were 0.02-0.05 microg/L and 0.1-0.2 microg/L, respectively. The saliva matrix effect was investigated. The method is rapid, simple, accurate and highly sensitive. The qualitative analysis and quantitative analysis of the collected saliva samples for the drugs can be finished within one hour, which is conducive to the rapid identification of the suspected drug addicts.