Serotonin (5HT) systems play important roles in brain development, and early perturbations of 5HT receptor expression produce permanent changes in 5HT synaptic function and associated behaviors. We exposed pregnant Rhesus monkeys to environmental tobacco smoke (ETS) during gestation and for up to 3 months postnatally and examined the expression of 5HT(1A) and 5HT(2) receptors, and of the presynaptic 5HT transporter in brain regions containing 5HT projections (frontal, temporal and occipital cortex) and cell bodies (midbrain). Perinatal ETS exposure elicited upregulation of 5HT(1A) receptor expression without parallel changes in the other two proteins, a pattern consistent with specific 5HT receptor dysregulation, rather than universal disruption of 5HT synaptic development. The effects seen here for ETS in a primate model are virtually identical in direction, magnitude and regional selectivity to those obtained previously for prenatal nicotine administration in rats. Specifically, early 5HT(1A) overexpression alters the program for future synaptic and behavioral 5HT responses, thus providing a mechanistic link for the shared effects of ETS and nicotine on a specific pathway responsible for behavioral anomalies associated with perinatal tobacco exposure. These results reinforce the need to reduce ETS exposure of pregnant women and young children.