OBJECTIVE To study the genetic association of interleukin-10 (IL-10) promoter polymorphisms in Southern Chinese patients with systemic lupus erythematosus (SLE), and to investigate possible associations with clinical manifestations of the disease. METHODS DNA was extracted from 88 Chinese patients with SLE and 83 ethnically matched controls. The IL-10 promoter region between positions -533 and -1120 was amplified by polymerase chain reaction, and polymorphisms were detected by restriction-enzyme cleavage. RESULTS No significant difference in the allele or haplotype frequencies between SLE patients and controls could be demonstrated. The *A and *C alleles at the -597 position were linked to the *T and *C alleles at the -824 position, respectively. However, when clinical features were examined, the *A allele at the -597 position and the *T allele at the -824 position were significantly associated with lupus nephritis, by chi-square analysis (P < 0.001, odds ratio 4.19, 95% confidence interval 2.02-8.71). Similarly, the haplotype -1087*A/-824*T/-597*A was also associated with renal involvement (P < 0.001, odds ratio 3.62, 95% confidence interval 1.80-7.31). CONCLUSIONS IL-10 promoter polymorphisms are not strong determinants of susceptibility to the development of SLE, per se, in Southern Chinese individuals. However, IL-10 genotypes are strongly associated with certain clinical manifestations of SLE and may have a role in predicting disease prognosis.