Inositol 1,4,5-trisphosphate (InsP3) mediates smooth muscle contraction by mobilizing intracellular calcium release. In this study we provide a direct comparison of the smooth muscle and brain InsP3 receptors in terms of InsP3 binding and primary structure. The KD for InsP3 binding for both receptors was found to be essentially the same. Sequences from 11 bovine smooth muscle receptor tryptic peptides (120 amino acids) were identified in the mouse brain receptor with two substitutions attributable to species differences. A cDNA (approximately 1-kilobase) encoding a portion of the mouse smooth muscle InsP3 receptor was cloned and found to be identical to that reported for the brain receptor. This cDNA was used as a probe to demonstrate that the approximately 10-kilobase InsP3 receptor mRNA is detected in brain, smooth muscle, heart, liver, and kidney but was not detected in skeletal muscle or skin.