Enkephalins have been implicated in the regulation of mood, anxiety, reward, euphoria and pain. One of the major enzymes for enkephalin degradation is neutral endopeptidase [enkephalinase, membrane metalloendopeptidase (MME)]. We identified a dinucleotide polymorphism in the 5' region of the MME gene. Subjects were placed into three genotypes, 3/3, 3/x, and x/x since the 3 allele was the most common of the six alleles. Using one-way analysis of variance, we examined the association of these genotypes with the mean SCL-90 scores for anxiety, depression, obsessive-compulsive and phobic anxiety symptoms in 120 Caucasian males from an addiction treatment unit. There was a significant association between the MME genotypes and the SCL-90 scores for phobic anxiety, obsessive-compulsive and anxiety at a Bonferroni corrected alpha value of 0.0125. These results support a role of genetic variants of enkephalin metabolism in anxiety.