Abstract Recent evidence demonstrates that neurons in sensory ganglia contribute to sensory signaling in both physiological and pathological states. In vivo sampling from this site may provide important insights into which substances mediate or modulate sensory transmission. To address this possibility, we have applied the microdialysis technique to the guinea pig trigeminal ganglia (TG). The large size and easy access of the TG in the guinea pig make it an ideal sampling site, while the somatotopic organization allows for specific regions of innervation to be studied at the ganglionic level. This report describes the use of microdialysis probes within the TG and use recovery and analysis of substance P (SP) and adenosine triphosphate (ATP) as case in points. Various physiological and pharmacological manipulations can be made, for example release of peptides from ganglionic neurons can be monitored in the presence or absence of inflammation in the orofacial region. Microdialysis performed in the TG thus provides a valuable site for recovery and measurement of a variety of extracellular substances that may be integral in the processing of trigeminal sensory information.