In view of a reported association between schizophrenia and the 5-HT2 receptor gene locus, as well as an association with treatment refractoriness at this locus, a case-control association study was conducted using a biallelic polymorphism. The distribution of the polymorphism was investigated among patients with schizophrenia (DSM-III-R, n = 174) and unaffected controls (n = 239). No significant differences in genotype distributions or allele frequencies were noted between the two groups. In support of the earlier report, a significant excess of individuals homozygous for allele C2 was noted among patients who responded unsatisfactorily to antipsychotic medication in comparison with the controls (odds ratio 1.78; 95% confidence intervals 1.06, 2.97). However, this difference was not significant following multivariate analysis. This study does not support an association between the 5-HT2 receptor gene locus and schizophrenia or subgroups based on treatment response.