Vitellogenin (VTG), a complex protein, is a precursor of yolk protein (lipovitellin and phosvitin) in all oviparous vertebrates studied to date. In amphibians, as in other oviparous vertebrates, VTG synthesis is hormonally dependent; estradiol-17 beta (E2) is especially important, although in vivo in the frog Rana esculenta the pituitary may be involved in hepatic VTG synthesis and secretion. The present in vitro experiments carried out during the main phases of the annual reproductive cycle of this frog showed that homologous pituitary homogenate (HPH), as well as E2, stimulated VTG synthesis in male and female livers, although their patterns of VTG secretion showed some differences with respect to the induction time and the rate of VTG secretion. The hepatic response to HPH occurred after a longer time than that of E2 VTG induction, and no cooperation between HPH and E2 was found in the VTG synthesizing response. It should be emphasized that during the refractory period (July), hepatic VTG synthesis in males and females could only be induced by HPH. These data demonstrate, for the first time, a direct action of HPH on VTG synthesis in male and female frog livers in all the periods tested; hepatic responsiveness to HPH and E2 varies with season and sex.