RNA-PLUS enables RNA isolation from tissues or cells of human, animal, plant, yeast or bacterial origin. RNA-PLUS represents an improvement on Chomczynski's procedure for single step RNA isolation providing higher efficiency removal of DNA and proteins. The method promotes formation of complexes of RNA with guanidinium and water molecules and abolishes hydrophilic interactions of DNA and proteins during sample extraction. RNAs obtained with RNA-PLUS are not degraded and are free of proteins and DNA. The RNA is suitable for all downstream applications including hybridization, northern, polyA mRNA isolation, in vitro transcription. 1 ml of reagent is sufficient for 50µg tissue or 5 x 106 cells.