Normal male rats display high levels of sexual activity when paired with sexually receptive females, a behavior regulated, in large part, by the medial preoptic area (MPOA). It has been documented that onset of c-fos proteins in the MPOA accompanies sexual behavior. Because prenatal stress (PS) demasculinizes sexual behavior in male rats, the present study examined whether such effects might be accompanied by a decrease in the neuronal activation in MPOA associated with sexual behavior. Adult prenatally stressed (P-S) and unstressed control males were paired with sexually receptive females, and sexual behavior allowed to commence. After a single mount, the pair was separated by a partition for the remainder of an hour, at the end of which the male was killed and the brain processed for c-fos immunocytochemistry; quantification was performed by means of computerized image analysis. P-S males expressed significantly less c-fos activity in the region of the MPOA, compared to nonstressed control males. Thus, the sexual deficits associated with P-S males may be due to a relative dearth of activity in the MPOA at the neuronal level. Coupled to earlier work showing decreased luteinizing hormone secretion in P-S males under similar conditions, the present data suggest a constellation of factors that contribute to PS-induced deficits in sexual behavior.