Anti-Saccharomyces cerevisiae antibodies (ASCA), directed against the phosphopeptidomannan (PPM) part of the cell wall of the yeast, have been identified as an important and specific serological marker for Crohn's disease. We evaluated the prevalence and properties of ASCA in APS patients. Thirty-one out of 155 APS patients tested positive for ASCA (20.0%), compared to 5.0% in healthy controls (P < 0.05). The presence of ASCA was not associated with any specific manifestation of APS. The ASCA found to be the population of anti-β2GPI antibodies (Abs). Affinity purified anti-β2GPI from ASCA-positive sera on a β2GPI column, bound specifically the PPM, as shownby direct binding and competition assays (95-98%). The PPM inhibited differentially the anti-β2GPI binding to β2GPI. Since the anti-β2GPI anti-PPM could bind only native form of β2GPI and not the recombinant form, we assume that these specific anti-β2GPI subpopulations of Abs are directed to the glycosylated site of the molecule. In conclusion, a subpopulation of anti-β2GPI is specific to the glycosylated site of the β2GPI molecule that cross-reacts with PPM.