BACKGROUND: Angiogenesis appears to be an important event in the pathophysiology of endometriosis (EM) and adenomyosis. Two angiogenic factors, fibroblast growth factor (FGF) 1 and 2, play a central role in the initiation of angiogenesis. We investigated whether FGF I -1385A/G and FGF2 754C/G polymorphisms are associated with a risk of developing EM and adenomyosis. METHODS: Genotypes were analyzed by the PCR restriction fragment length polymorphism method in two groups of women, of Han ethnicity in north China, aged 16-55 years: (1) 421 EM patients and 421 controls; (2) 269 adenomyosis patients and 269 controls. RESULTS: There was no difference in genotype distribution of the FGFI -1385A/G polymorphism between adenomyosis cases and controls (P > 0.05), but the frequency of the A allele in EM patients was lower than that in controls (P = 0.013). Genotype and allele frequencies of the FGF2 754C/C polymorphism were significantly different in both EM and adenomyosis cases versus control groups. Compared with C/C homozygotes, the G allele (C/G + G/G) was associated with a decreased susceptibility to developing EM [odds ratio (OR) = 0.575, 95% confidence interval (CI) = 0.387-0.854] and adenomyosis (OR = 0.577, 95% Cl = 0.367-0.906). Combined genotype analysis of both polymorphisms also showed differences between cases versus controls (all P < 0.001). CONCLUSIONS: Our study shows for the first time that the FGF2 754C/G polymorphism may be associated with a risk of developing EM and adenomyosis in north Chinese women. Carriers of the G allele in the FGF2 gene appear to be protected from these gynecological diseases. Further studies in other populations, and of other candidate genes, are now warranted.