We have recently reported that natural antibodies against phosphorylcholine (anti-PC) have atheroprotective properties. Here we compare anti-PC with other autoantibodies in SLE patients with and without cardiovascular disease (CVD). Twenty-six women (52 +/- 8.2 yrs) with SLE and a history of CVD (SLE cases) were compared with 26 age-matched women with SLE without CVD (SLE controls) and 26 age-matched population-based control women (controls). PC was conjugated with BSA (PC-BSA) or keyhole-limpet haemocyanin (PC-KLH). Anti-PC and antibodies against phosphatidylserine (anti-PS) and BSA (anti-BSA) were studied by ELISA. Anti-PC-IgG were extracted from intravenous immunoglobulin (IVIG). Activation of endothelial cells by platelet-activating factor (PAF) was studied with FACScan. IgG anti-PC-BSA and anti-PC-KLH were decreased among SLE-cases and SLE-controls as compared with controls (P < 0.005 and P < 0.05), respectively. SLE cases were more prevalent in the lowest 25th percentile of anti-PC-IgM (and IgG) as compared with controls (P < 0.05) but anti-PC-IgM levels did not differ significantly between groups. Among SLE controls, anti-PC-BSA were associated negatively with organ damage (SLICC) and disease activity (SLEDAI) (P < 0.05). Among SLE cases, anti-PC-BSA and anti-PC-KLH were associated negatively with SLICC (P = 0.021; P = 0.010) and anti-PC-BSA was negatively associated with SLEDAI (P < 0.039). Anti-PS-IgG and anti-BSA-IgG were raised among SLE cases as compared with other groups (P < 0.05) and did not cross-react with anti-PC. Anti-PC-IgG could be extracted from IVIG and inhibited PAF-induced expression of adhesion molecules. Low levels of anti-PC could be of importance in SLE. Anti-BSA and anti-PS and low levels of anti-PC could contribute to development of CVD in SLE.