The Schlafen gene family has been implicated in lymphoid and myeloid maturation and differentiation as well as inflammation. However, little is known about the functions of this gene family except that anti-proliferative activities, particularly for Schlafen1, the prototype member of the family, have been reported. This was shown mainly by ectopic expression of Schlafen1 in murine fibroblasts resulting in growth inhibition and a G1 cell cycle arrest apparently via repression of Cyclin D1 expression. However, we have been unable to reproduce these findings. Schlafen1 and Schlafen2 failed to inhibit cell proliferation, cause G1 cell cycle arrest, or affect Cyclin D1 level in murine fibroblasts. This was regardless of whether overexpression was constitutive, induced or from transient transfections. Moreover, in our hands, Schlafen1 and -2 do not appear to regulate the activity of Cyclin D1 promoter. Importantly, we also showed that Schlafen1 and -2 do not play anti-proliferative roles in more physiologically-relevant myeloid cell lines. We therefore suggest that Schlafen1 and Schlafen2 might not have obligatory anti-proliferative activities, at least in vitro, and that efforts to explore their functions should be directed to other aspects, such as haemopoietic development and immune response.