In previous studies using specific G alpha(s) antibodies we have identified several human myometrial G alpha(s) protein isoforms with molecular masses of 45, 46, 47, 54, and 58 kDa, respectively. During pregnancy, levels of the 46- and 54-kDa proteins are significantly increased compared to those in nonpregnant myometrium and then decreased at the onset of labor. In this study we investigated the expression of G alpha(s) messenger ribonucleic acid (mRNA) splice variants, which are generated as a result of alternative splicing of a single mRNA precursor, in term pregnancy and parturition to determine whether there was any correlation with the observed changes in G alpha(s) protein isoforms. A myometrial G alpha(s) complementary DNA was synthesized using RT-PCR and cloned into pCR(tm)II suitable for preparation of riboprobes for use in ribonuclease protection assays. Using this technique, we identified at least three myometrial G alpha(s) mRNAs, including two forms of G alpha(s)-Large (with or without the serine at amino acid 87) and one form of G alpha(s)-Small (with the serine at amino acid 72). G alpha(s)-Small (with the serine) and G alpha(s)-Large (with the serine) mRNAs encode for the 46- and 54-kDa G alpha(s) protein isoforms, respectively, and were increased in term pregnancy and then subsequently decreased after the onset of labor. Our data suggest that posttranscriptional regulation of G alpha(s) mRNAs may be important in the differential expression of G alpha(s) protein isoforms during pregnancy and labor.