OM-89 (Subreum), an E. coli extract, is used clinically in the treatment of rheumatoid arthritis. In this study, the authors examined the effect of OM-89 on some aspects of SLE in the murine model MRL-lpr/lpr. Animals were given OM-89 orally at a dose of 400 mg/kg weight (40 mg active substance) 5 d a week from six weeks old. It was found that mice receiving the drug reached the point of 55% (6/11) survival at the age of 33 weeks compared with 27 weeks for the control group (54%; 7/13). There was a significant increase in the delay before developing alopecia in the treated group (P < 0.01). The increase in proteinuria in the control group was significantly higher than in the treated group (P < 0.03). In a second set of experiments sacrificing the animals at week 22, a significant decrease in anti-dsDNA auto-antibodies was also found in the treated group (P < 0.05), histopathologically a less severe tubular destruction in the kidney was observed in the treated group. It can be concluded that the oral treatment of OM-89 can significantly reduce the severity of SLE in this strain of mice. It can be postulated that the administration of the bacterial extract could modulate the immune response, modifying the Th1 and Th2 balance and inducing oral tolerance.