Autism is a pervasive neurodevelopmental disorder, with a significant role of genetic factors in its development. The neuropilin-2 (NRP2) gene is localized to 2q34, an autism susceptibility locus. NRP2 has been demonstrated to both guide axons and to control neuronal migration in the central nervous system. It has been reported that NRP2 may be required in vivo for sorting migrating cortical and striatal interneurons to their correct destination. We examine the association between the NRP2 gene and autism using a cohort of 169 Chinese Han family trios. Four single nucleotide polymorphisms (SNPs) were genotyped by the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analyses. The transmission disequilibrium tests (TDT) of SNPs and haplotype association were carried out using the TDTPHASE program. We found significant genetic association between autism and two of the SNPs of the NRP2 gene (rs849578: P = 0.017, rs849563: P = 0.027), as well as specific haplotypes, especially those formed by rs849563. Furthermore, haplotypes constructed with all markers showed significant excess transmission in both global and individual haplotype analyses (P = 0.004 and 0.017, respectively). The polymorphisms in the NRP2 gene are associated with autism, implying that the NRP2 gene may render individuals to be predisposed to autism. © 2007 Wiley-Liss, Inc.