THE platelet-activating factor PAF (l-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent lipid first messenger active in general cell activation, fertilization, inflammatory and allergic reactions, asthma, HIV pathogenesis, carcinogenesis, and apoptosis^1–5. There is substantial evidence that PAF is involved in intracellular signalling, but the pathways are poorly understood. Inactivation of PAF is carried out by specific intra- and extracellular acetylhydrolases⁶ (PAF-AHs), a subfamily of phospho-lipases A2 that remove the sn-2 acetyl group. Mammalian brain contains at least three intracellular isoforms, of which PAF-AH(Ib) is the best characterized^7–9. This isoform contains a heterodimer of two homologous catalytic subunits α₁ and α_2,, each of relative molecular mass 26K, and a non-catalytic 45K β-subunit, a homologue of the β-subunit of trimeric G proteins. We now report the crystal structure of the bovine α₁ subunit of PAF-AH(Ib) at 1.7 Å resolution in complex with a reaction product, acetate. The tertiary fold of this protein is closely reminiscent of that found in p21^ras and other GTPases. The active site is made up of a trypsin-like triad of Ser 47, His 195 and Asp 192. Thus, the intact PAF-AH(Ib) molecule is an unusual G-protein-like (α₁/α₂)β trimer.