Many cytokines, including transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha), are involved in the inflammatory process of Henoch-Schönlein purpura (HSP). The objective of this study was to investigate whether TGF-beta C-509T and TNF-alpha G-308A polymorphisms are associated with childhood HSP. The loci of interest were amplified from genomic DNA using specific primers and polymerase chain reaction, and these two polymorphisms were compared between Chinese children with HSP and healthy controls. The disease severities evaluated and expressed as symptom score of patients with different genotypes were also compared. The TGF-beta -509 TT genotype was more common in children with HSP than controls (31% vs. 8%, P =0.03, odds ratio=4.95). The allelic frequencies of TGF-beta -509, genotypic and allelic frequencies of TNF-alpha -308 were not significantly different. Patients with the TT genotype had more severe clinical presentations than non-TT (TC+CC) patients (4.1+/-0.42 vs. 2.7+/-0.31, P =0.018). These results suggest that the TT genotype of the C-509T polymorphism of the TGF-beta gene might be related to the susceptibility of Chinese children to HSP and to the severity of this disease.