The regulation of the phospholipase C (PLC) and the expression of inositol 1,4,5-trisphosphate receptors (IP₃Rs) in terms of mRNA, proteins, and binding capacity were examined in the rat myometrium and endometrium at midgestation (Day 12) and at term (Day 21) comparatively to the estrogen-treated tissues (Day 0). In both uterine tissues, the production of inositol phosphates mediated by carbachol as well as by AlF₄⁻ was enhanced with advancing gestation. ³[H]IP₃ binding sites in membranes also increased during pregnancy (Day 21 > Day 12 > Day 0). The mRNAs encoding for three isoforms of IP₃R as well as their corresponding proteins, IP₃R-1, IP₃R-2, and IP₃R-3 were coexpressed, albeit to different extents, in the myometrium and endometrium. The expression of IP₃Rs increased with advancing gestation, except for IP₃R-2 that increased only in the endometrium at term. Thus, the pregnancy-related upregulation of the PLC cascade coincided with an increase in the expression of IP₃Rs. The difference noted between the two uterine tissues suggests that IP₃Rs may have cell-specific functions.