Since 1983 we have followed a total of 165 patients with antiphospholipid syndrome (APS). During the median followup period of 78 mo (range 12-336 mo), 3 of 80 patients with primary APS subsequently developed features of systemic lupus erythematosus (SLE) or lupus-like disease. One patient developed lupus-like disease 4 yrs and the other 2 developed full blown SLE more than 10 yrs after initial presentation of primary APS. Tissue typing in patients who developed SLE showed HLA antigens A2, A3, B35, Bw6, Cw4, DR7, DRw53, and DQ2 (Case 2); and A1, A3, B7, B8, Bw6, Cw7, DR4, DR15, DR51, DRw53, and DQ1 (Case 3). We report clinical features and genetic associations of these 3 patients.