The aim of this study was to investigate in vitro the pharmacologic properties of rabbit esophageal muscularis mucosae. Stimulation of its motor innervation elicited only atropine-sensitive excitatory responses. This tissue was not refractory to histamine but appeared to be rapidly desensitized to its effects. Responses to adrenoreceptor agonists were produced by excitatory alpha(1) and beta(1) adrenoreceptors, inhibitory beta(3) receptors but not alpha(2) receptors. The esophageal muscularis mucosae was only weakly stimulated by neurokinins and bradykinin, and these responses were mediated via NK2, NK3, B1, and B2 receptors, respectively. Adenosine diphosphate and adenosine triphosphate produced approximate to 40% maximal contractions through the activation of P2 receptors, whereas adenosine monophosphate and adenosine were without effect. Responses to prostaglandins E-2 and F-2 alpha were less than or equal to 10% of the tissues' maximum response to acetylcholine. These data demonstrate that rabbit esophageal muscularis mucosae has a simple excitatory innervation and is only weakly stimulated by a variety of pharmacologic agents. For these reasons it is distinct from muscularis mucosae found elsewhere in the rabbit gastrointestinal tract.