The regulator of the G‐protein signaling 4 (RGS4) gene was shown to have a different expression pattern in schizophrenia patients in a microarray study. A family‐based study subsequently implicated the association of this gene with schizophrenia. We replicated the study with our sample from the Irish Study of High Density Schizophrenia Families (ISHDSF). Single marker transmission disequilibrium tests (TDT) for the four core SNPs showed modest association for SNP 18 (using a narrow diagnostic approach with FBAT P = 0.044; with PDT P = 0.0073) and a trend for SNP 4 (with FBAT P = 0.1098; with PDT P = 0.0249). For SNP 1 and 7, alleles overtransmitted to affected subjects were the same as previously reported. Haplotype analyses suggested that haplotype G‐G‐G for SNP1–4–18, which is the most abundant haplotype (42.3%) in the Irish families, was associated with the disease (narrow diagnosis, FBAT P = 0.0061, PDT P = 0.0498). This was the same haplotype implicated in the original study. While P values were not corrected for multiple testing because of the clear prior hypothesis, these results could be interpreted as supporting evidence for the association between RGS4 and schizophrenia. © 2004 Wiley‐Liss, Inc.