About 30% of male infertility cases can be explained by either chromosome alterations or mutations in genes functioning in the male germ line. Many genes are suspected for their possible role in male infertility. So far, only microdeletions in the azoospermia factors (AZF) region and mutations in the Cystic Fybrosis Transmembrane Conductance Regulator (CFTR) gene have been clearly correlated with defects in spermatogenesis. Recent data have suggested that mutation C677T in the methylentetrahydrofolate reductase (MTHFR) gene might play a role in infertility. The C677T mutation causes hiperhomocysteinemia, which might be responsible for precocious atherosclerosis of the testicular arteries. We analyzed 52 infertile men and 47 men with at least one child as control subjects. All subjects were genotyped for MTFHR C677T by PCR-RFLP analysis. Among patients, 11.5% (6/52) were homozygous and 46.2% (24/52) were heterozygous for C677T. In control group, 12.8% (6/47) were homozygous and 46.8% (22/47) were heterozygous. Frequency of homozygotes for C677T mutation did not differ significantly between the two groups (P=0.882). We speculate that overall enrichment of folates could nullify or minimize the effect of this mutation. However, this hypothesis deserves further confirmation on a larger number of patients. The role of other genes, which could act in combination with MTHFR, should also be taken into consideration.