In Rana temporaria, previous results, obtained in animals with hypothalamic islands, have shown that the gonadotropic activity of the pars distalis of the hypophysis is controlled by the pars ventralis of the tuber cinereum. As the pars distalis is not innervated by the brain, this control must be exerted via a humoral pathway, by means of releasing factors produced by the pars ventralis tuberis. In this paper, the comparison is made between (1) the results obtained in a first group of female animals in which total operative interruption of all neural connections between the pars ventralis tuberis and the median eminence-hypophysis persisted and (2) the results of a second group of female animals in which, after identical operation, regeneration of the interrupted neural connections had occurred. In both groups, the blood supply of the neural isolated median eminence-hypophysis was preserved and normal circulation of the cerebrospinal fluid was only temporarily disturbed by operation. In the first group, seasonal development of the ovaries and of the oviducts remained completely absent while, in the second group, development of the ovaries and of the oviducts occurred. As the difference between the two groups only consisted in either the presence or the absence of (regenerated) nerve fibres between the pars ventralis tuberis and the median eminence-hypophysis, it is concluded that the control of the gonadotropic activity of the pars distalis by the pars ventralis tuberis is mainly exerted via a neurosecretory axonal pathway to the hypophysial portal system and not via the cerebrospinal fluid. This conclusion is supported by electron microscopic studies which revealed the existence of a tubero-hypophysial peptidergic neurosecretory system.