Despite its importance for development, relatively little is known about how allelic variation interacts with both pre- and postnatal stress. We examined the interaction between serotonin transporter (5-HTT) genotype, prenatal and postnatal stress on glucocorticoid receptor (GR) mRNA expression, corticosteroid stress responses, and behavior in adult male rats. Prenatal stress involved a daily restraint of pregnant dams from gestational Day 10-21. Postnatal stress involved raising pups after parturition either by their mothers (MR) or in the artificial rearing (AR) paradigm, with or without additional "licking-like" stroking stimulation. 5-HTT genotype, hippocampal GR mRNA level, corticosteroid stress response, and behaviors including startle response, prepulse inhibition (PPI), and locomotor activity were measured in adult male rat offspring. We found significant genotype by prenatal stress interactions for hippocampal GR mRNA levels and for the corticosterone stress responses in adulthood. In contrast, behavioral endpoints tended to be more clearly affected by an interaction between genotype and postnatal environment. These findings suggest that allelic variation in the 5-HTT gene interacts with the prenatal environment to affect the hypothalamic-pituitary-adrenal (HPA) axis physiology and the postnatal environment to affect behavior. These results are the first to indicate a role for genetic variation in the 5-HTT gene in physiology and behavior in the rat.