In previous studies we have shown that relaxin (RLX), a peptide hormone produced predominantly during pregnancy, is a powerful inhibitor of platelet aggregation. The current study shows that RLX, given systemically to rats, also affects the number of circulating platelets and their release by spleen megakaryocytes. Male albino rats were treated acutely or chronically with RLX, and the effects of the peptide evaluated by platelet count and morphological analysis of spleen megakaryocytes. The results obtained show that RLX causes a decrease of circulating platelets, which is already appreciable 1 h after a single administration and becomes significant upon a May treatment with the peptide (790000 ± 18000/ml in the RLX-treated rats versus 865 000 ± 23 000/ml in the controls; P<0.01). Coincidentally, spleen megakaryocytes show clearcut changes consistent with a depression of platelet release, namely the appearance of a thick peripheral cytoplasmic halo, filled with actin microfilaments and without platelet territories, and a virtual absence of images of thrombocytopoiesis. Based on the properties of RLX in inhibiting hemostasis, recognized in previous investigations and further proved by the present study, a role of the peptide is proposed in counteracting the hypercoagulable state which currently takes place during normal pregnancy.