The dopamine system has long been suspected of aetiological involvement in schizophrenia because of a number of lines of evidence pointing to excess dopaminergic activity in the illness. Recently, negative allelic association was reported between a single base deletion in the promoter region of the DRD2 gene, -141 delta C, and schizophrenia, with an odds ratio of 0.60. This was of particular interest since the deletion, which occurs in about 22% of the Japanese population, is functional in that it results in reduced (20-40% of wild-type) basal levels of receptor expression. We have examined this polymorphism in 229 family trios from SW China, consisting of both parents and a single offspring affected by schizophrenia, and 151 Caucasian cases with schizophrenia and 145 Caucasian normal controls from the UK. Using the haplotype-based haplotype relative risk method (HHRR), the frequency of the -141 delta C allele was 6.9% in the affected Chinese subjects compared to an estimated frequency of 9.0% in this population (chi 2 = 1.21, 1 df, ns), with an odds ratio of 0.76 (95% CI 0.46-1.25). Using the transmission disequilibrium test, we likewise found no evidence for linkage or linkage disequilibrium with this polymorphism (chi 2 = 0.94, 1 df, ns). In the Caucasian cases, the frequency of the -141 delta C was 13% compared to 10% in controls (chi 2 = 1.57, p = 0.21) with an odds ratio of 1.39 (95% CI 0.81-2.40). We thus conclude that the DRD2 -141 delta C polymorphism is less frequent in Chinese and Caucasian populations (9%) than in Japan (22%) and is not a significant risk factor for schizophrenia in our populations. The -141 delta C allele remains a strong candidate for a variety of other traits and diseases, including reward-related behaviours such as drug abuse, which have been associated with the dopamine system.