A single nucleotide polymorphism of the neuregulin 1 gene (SNP8NRG243177/rs6994992) increases the risk of psychosis, affects prefrontal activation and structural connectivity in the brain, and is related to the expression of a specific neuregulin 1 isoform. The purpose of this study was to investigate the interaction between this polymorphism and reactivity to psychosocial stress. Two hundred patients with schizophrenia were genotyped. The patients and one of their family members participated in neutral and conflict-related interactions in which the number of relatives' criticisms and patients' unusual thoughts was assessed. Patients with the risk T/T genotype expressed more unusual thoughts than C-carriers (C/T and C/C) during conflict-related interactions but not during neutral interactions. Two controls polymorphisms of the neuregulin 1 gene (rs10954867 and rs7005288) showed no such effect. These results raise the possibility that there is a significant gene by environment interaction regarding SNP8NRG243177/rs6994992 and psychosocial stress. © 2008 Wiley-Liss, Inc.