OBJECTIVE Both adverse social environments and genetic factors contribute to loneliness in old age. Mixed findings between older adults' social relations with their children and their levels of loneliness suggested that a gene × social environment interaction may be operating. We examine whether the effects of infrequent contact with children and low levels of perceived social support from children on loneliness in older adults are moderated by two candidate single nucleotide polymorphisms (i.e., rs1876831 and rs242938) in the corticotrophin releasing hormone receptor 1 (CRHR1) gene. METHODS This was a longitudinal observational study. METHODS and METHODS A population-based sub-sample of 1,374 community-dwelling older adults aged 65 years and older was examined from both the 2003-2004 and 2006-2007 English Longitudinal Study of Aging assessments. METHODS Our main outcome measure is loneliness, which was assessed by four items extracted from the ULCA loneliness scale. RESULTS Compared with older adults carrying the CT/TT genotypes, individuals homozygous for the C allele of rs1876831 reported higher levels of loneliness in the context of infrequent social contact with children and lower levels of perceived social support from children. No gene × social environment interactions were found for loneliness between rs242938 and an adverse social environment related to children. CONCLUSIONS This study provides the first evidence in humans that the CRHR1 gene interacts with exposure to a negative social environment to predict loneliness in older adults.