Isolated olfactory cilia from the channel catfish (Ictalurus punctatus) exhibited phosphatidylinositol-4,5-bisphosphate phosphodiesterase (E.C.3.1.4.11) activity. The phosphodiesterase activity was stimulated in the presence of an odorant for the catfish, namely the amino acid L-alanine. The enzyme activity was also stimulated in the presence of GTP and its nonhydrolyzable analogues. The activation of the phosphodiesterase by guanine nucleotides, in combination with the identification of guanine nucleotide-binding protein(s) in the isolated cilia, indicate the probable participation of a guanine nucleotide-binding protein in stimulation of phosphoinositide turnover in the olfactory receptor neuron.