TO investigate the possible role of 5HT1B and/or 5HT1D receptors in controlling neurogenic inflammation, we performed a co-localization study of the mRNA for 5HT1B and 5HT1D receptors and of substance P or calcitonin gene-related peptide (CGRP) mRNA in the guinea pig trigeminal ganglion using double labelling in situ hybridization techniques. The 5HT1D receptor mRNA is abundant whereas 5HT1B receptor mRNA is scarce. The vast majority of cells containing substance P mRNA also contained 5HT1B receptor mRNA, but very few cells expressed substance P mRNA and 5HT1D receptor mRNA. Both receptor mRNAs were co-localized with CGRP mRNA. Hence, 5HT1D receptors may control the release of CGRP only, whereas 5HT1B receptors may control the release of both substance P and CGRP. The question remains whether selective 5HT1D agonists will have migraine abortive properties.