We describe a patient with primary antiphospholipid syndrome (PAPS) and haemolytic anemia with cryoagglutinins, in whom antibodies eluted from red blood cells (RBC) displayed anti-cardiolipin (CL) binding activity. This activity was confined to the IgG isotype and was directed to the negatively-charged phospholipids only. In addition, the patient's IgG fraction displayed a higher binding to RBC in comparison to normal control IgG and this reactivity was inhibited after absorption of the anti-CL activity with CL-micelles. These findings further sustain the association between antiphospholipid antibodies (APA) and Coombs' positivity with or without haemolytic anemia and suggest that APA could be at least in part responsible for anti-RBC activity.