Objective: Neurons of the respiratory network in the brainstem express a variety of serotonin receptors (5-HTRs) that are mostly operating on adenylyl cyclase. The exception to that rule is the 5-HT2 receptor family comprised of 5-HT2A, 5-HT2B, and 5-HT2CRs which are directed towards protein kinase C (PKC). While 5-HT2AR expression within the respiratory network and systemic function in vivo has been studied extensively, the functions of 5-HT2BRs are still unclear. 5-HT2Rs use a Gq- mediated signaling sequence leading to activation of phospholipase C and IP3/DAG pathways. This signal pathway implies an excitatory action of 5-HT2R-agonists on respiration. Methods: To demonstrate receptor expression at the protein level within pontine and medullary nuclei of the respiratory network we used commercially available 5-HT2AR antibodies as well as a new anti-5-HT2BR antibody. Using the working heart-brainstem preparation we studied the effects of systemic application of selective agonists and antagonists for 5-HT2ARs and 5-HT2BRs on the spontaneous breathing activity of rats. Results: Given seperately the drugs evoked significant changes of breathing, with 5-HT2BR being the dominant receptor when stimulated together with simultaneous application of both agonists. Conclusion: All findings suggest a significant role of both receptors in cardio-respiratory function.