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-beta2GPI antibodies (Abs). Affinity purified anti-beta2GPI from ASCA-positive sera on a beta2GPI column, bound specifically the PPM, as shown by direct binding and competition assays (95-98%). The PPM inhibited differentially the anti-beta2GPI binding to beta2GPI. Since the anti-beta2GPI anti-PPM could bind only native form of beta2GPI and not the recombinant form, we assume that these specific anti-beta2GPI subpopulations of Abs are directed to the glycosylated site of the molecule. In conclusion, a subpopulation of anti-beta2GPI is specific to the glycosylated site of the beta2GPI molecule that cross-reacts with PPM.