Endometriosis is defined as a condition in which tissue histologically similar to the endometrium is found outside the uterine cavity. It develops mostly in women of reproductive age. Endometriosis shows a drastically elevated frequency in industrial areas. GSTM1 gene encodes a major detoxification phase enzyme that helps detoxify various xenobiotics. Deficiency in GSTM1 activity is caused by homozygous deletion of GSTM1 and leads to various biological consequences. There are significant interethnic differences in GSTM1 allele frequencies. In this study, the relationship between GSTM1 genotypes and endometriosis in an Iranian population was investigated. The study included 120 patients and 200 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients and healthy controls using polymerase chain reaction (PCR). The GSTM1 null genotype was significantly associated with the increased risk of endometriosis (OR=3.75, 95% confidence interval (CI)=2.42-6.45, P<0.0001). The prevalence of GSTM1-null genotype in the patient group was 72.5%, compared to 40% in the control group. The proportion of GSTM1A/B genotype was higher in controls as compared to cases (20% vs. 2.5%). This study suggests that GSTM1 null genotype is associated with higher risk of endometriosis; these observations, however, requiring further confirmation in a larger multi-ethnic study.