Owing to their agonist action on dopaminergic systems, cannabinoids may play a major role in substance dependency and schizophrenia. We examined the (AAT)n triplet repeat polymorphism nearby the CNR1 gene, which encodes human cannabinoid (CB1) receptor, in a male Afro-Caribbean population. The allelic and genotypic distributions were significantly different in non-schizophrenic cocaine dependents (n = 97), schizophrenic cocaine dependents (n = 45) and matched controls (n = 88) (P < 10(-4)). The frequency of the (AAT)12 repeat allele was increased in non-schizophrenic cocaine dependents and schizophrenic cocaine dependents vs controls (25.3 and 26.7 vs 5.7%) (P < 10(-4)). Our results support that the (AAT)n polymorphism nearby the CNR1 gene could be associated with predisposition to cocaine dependency.