Recent studies have suggested that heterogeneity in the level of dopamine activity and function might be useful for identifying a subgroup of cocaine-dependent patients responding better to dopamine-enhancement pharmacotherapy. Here we hypothesized that response to levodopa/carbidopa treatment would be greater in patients with genetically determined low levels of the dopamine metabolizing enzyme dopamine β-hydroxylase (DβH). Seventy-one cocaine-dependent patients who participated in a 12-week randomized double-blind placebo-controlled trial of levodopa/carbidopa were genotyped for the DβH gene (DBH) polymorphism rs1611115. Our results showed that for patients with the low DβH activity genotypes (CT/TT) who received levodopa, the odds of having cocaine-positive urine decreased significantly over treatment compared with placebo-treated patients with the CT/TT genotypes (P=0.004). Individuals with the normal DβH activity genotype (CC) showed no differential response to levodopa. These preliminary results need to be confirmed in a larger sample focusing on the DBH polymorphism.