It has recently been proposed that guanine nucleotide (GTP)-binding proteins (G-proteins) are involved in transducing stimuli in olfactory receptor neurons. If this is the case, G-proteins should be expressed when receptor cells first generate action potentials in response to odorants, i.e. in the rat fetus on the 16th embryonic day (E16). We have done an immunohistochemical study to determine when the alpha- and beta-subunits of the stimulatory G-protein (Gs), are expressed in developing rat olfactory epithelium. The 3 primary antisera used were monospecific polyclonal antibodies generated in rabbits by immunization with synthetic peptides, the amino acid sequences of which matched a portion of the alpha- or beta-subunits of stimulatory G-protein. Both subunits were present in olfactory axons at E15 and in olfactory receptor cell cilia at E16, the day when cilia first sprout in these cells. As development progressed and more cilia grew, most were immunoreactive with antisera to both subunits. Examination of specimens with electron microscopic immunocytochemistry confirmed the localization. Not all cilia on a given olfactory cell were stained, in either fetal or juvenile specimens. The observation that G-proteins are expressed in cilia when action potentials are first demonstrated supports the hypothesis that G-proteins are involved in signal transduction in olfactory receptor cells.