cDNAs for the bovine alpha 1A-, hamster alpha 1B- and rat alpha 1D-adrenoceptors (AR) were transfected into human embryonic kidney 293 (HEK293) cells by calcium phosphate precipitation and stably expressed at high levels. The inositol phosphates (InsPs) accumulation was measured by the method of 3H-inositol incorporation and column chromatography. Susceptibilities to the desensitization of alpha 1-AR subtypes-mediated InsPs accumulation were determined in HEK 293 cells stimulated sustainedly by norepinephrine (NE). The NE-induced InsPs accumulation showed progressive decrease by NE pretreatment with increasing time of preincubation and concentration of NE in the cells transfected with all the alpha 1-AR subtypes. However, susceptibilities to the desensitization were different among the three subtypes. The desensitization of alpha 1A-AR took place earliest and needed lowest concentration of NE. The desensitization of alpha 1D-AR appeared to be the latest and needed hightest concentration of NE, while alpha 1B-AR stood in between.