In the tilapia species Oreochromis niloticus, the pituitary releases two forms of prolactins (tiPRL(188) and tiPRL(177)) The binding parameters and the activation of tiPRL-induced JAK2/Stat5 signalling pathway were analysed using a mammalian cell line transiently transfected with the tiPRL receptor (tiPRLR). Our data indicate that the tiPRLR is able to mediate transcriptional activation of the PRL responsive element, At nanomolar concentrations, tiPRL(188) activates gene transcription whereas at micromolar concentrations it inhibits luciferase transcription from the lactogenic responsive element. This is consistent with a model of receptor dimerisation, In contrast, the activation by tiPRL177 was only reached at high (mu M) concentrations. The transcriptional activities induced by tiPRL(177) and tiPRL(188) are discussed in the context of the physiology of these hormones.