The characterization and relevance of the neuroendocrine response to sexual activity in humans is poorly understood. We therefore developed a model to continuously record the neuroendocrine response to various forms of sexual stimulation in plasma. Besides transient activation of the sympathoadrenal system, the main finding in this series of studies is that there is a substantial, long-lasting increase in plasma prolactin concentrations following orgasm (masturbation and coitus conditions) in men and women, but unchanged prolactin levels following sexual arousal without orgasm. The theoretical model we used hypothesizes that the orgasm-induced prolactin release modifies different dopaminergic systems within the CNS that are responsible for sexual appetence and refractoriness. This was supported by subsequent studies demonstrating that comparatively small changes in pharmacologically altered prolactin levels have an acute effect on sexual appetence and performance. To further elucidate the role of prolactin and catecholamines in regulating sexual appetence and function, our current study continuously analyzed neurochemical parameters in lumbar cerebrospinal fluid (CSF) via spinal catheterization; this included prolactin, biogenic amines and their metabolites during the sexual response cycle. Comparable to peripheral mechanisms, norepinephrine increased in CSF during audiovisually/masturbation-induced sexual arousal and orgasm and remained elevated for the remainder of the session. In contrast, none of the other measures, in particular prolactin and dopamine or its metabolites, depicted significant alterations. In conclusion, the human sexual response cycle is characterized by an increase in sympathoadrenal activity in CSF/plasma and by a pronounced secretion of plasma prolactin after orgasm. However, analysis of lumbar CSF is not able to detect dopaminergic or peptidergic activity possibly due to due to local and restricted release in diencephalic and mesencephalic brain regions.