1. Smooth muscle from six sites in the cat gastrointestinal tract was evaluated with respect to its ability to generate contractions in calcium-free solutions.
2. Membrane depolarization and carbachol, but not cholecystokinin or neurotensin, increased tension in smooth muscle segments of esophagus, corpus, duodenum, ileum, proximal colon and distal colon in calcium-free solution.
3. Substance-P produced a contractile response in the absence of calcium but only in the corpus and distal colon.
4. These findings indicate that peptide mediated release of intracellular calcium plays a minimal role in activation of cat gastrointestinal smooth muscle.