OBJECTIVE: To examine the relationships among the variable number of tandem repeats in the monoamine oxidase-A linked polymorphic region allelic variation (MAOA-uVNTR) and the symptoms of depression and sleep quality. The monoamine oxidase-A (MAOA) gene, which plays a vital role in degradation of neurotransmitters such as serotonin, norepinephrine, and dopamine, contains a polymorphism in its promoter region (MAOA-uVNTR) that affects transcriptional efficiency. MAOA-uVNTR genotype has been associated with both psychological and physical measures. METHODS: The sample consisted of 74 males enrolled in a case/control study of caregivers for relatives with dementia. Age- and race-adjusted linear regression models were used to examine the association between low versus high MAOA-uVNTR activity alleles, symptoms of depression (Center for Epidemiological Studies of Depression), and sleep quality ratings (Pittsburgh Sleep Quality Index). RESULTS: MAOA-uVNTR alleles associated with less transcriptional activity were related to increased symptoms of depression (p < .04; Cohen's d = 0.52) and poorer sleep quality (p < .04; Cohen's d = 0.31). CONCLUSIONS: Individuals with less active MAOA-uVNTR alleles may be at increased risk for depressive symptoms and poor sleep.