<i>Background/Aims:</i> Recent studies have implicated a region on chromosome 1q21-23, including the <i>NOS1AP</i> gene, in susceptibility to schizophrenia. However, replication studies have been inconsistent, a fact that could partly relate to the marked psychopathological heterogeneity of schizophrenia. The aim of this study is to evaluate association of polymorphisms in the <i>NOS1AP</i> gene region to schizophrenia, in patients from a South American population isolate, and to assess if these variants are associated with specific clinical dimensions of the disorder. <i>Methods:</i> We genotyped 24 densely spaced SNPs in the <i>NOS1AP</i> gene region in a schizophrenia trio sample. The transmission disequilibrium test (TDT) was applied to single marker and haplotype data. Association to clinical dimensions (identified by factor analysis) was evaluated using a quantitative transmission disequilibrium test (QTDT). <i>Results:</i> We found significant association between eight SNPs in the<i> NOS1AP</i> gene region to schizophrenia (minimum p value = 0.004). The QTDT analysis of clinical dimensions revealed an association to a dimension consisting mainly of negative symptoms (minimum p value 0.001). <i>Conclusions:</i> Our findings are consistent with a role for <i>NOS1AP</i> in susceptibility to schizophrenia, especially for the ‘negative syndrome’ of the disorder.