Disclosed are novel proteins, referred to as megakaryocyte growth and development factors (MGDFs; also generally referred to as Mpl ligands), that have a biological activity of stimulating the growth of megakaryocytes and augmenting the differentiation or maturation of megakaryocytes, ultimately to result in the production of platelets. MGDF derivatives comprising MGDF molecules attached to water soluble polymers, such as polyethylene glycol, are also disclosed, along with methods for their preparation. The MGDF proteins and derivatives are useful in methods for treating mammals to increase platelets and/or megakaryocytes. Also disclosed are processes for obtaining the MGDFs in homogeneous form from natural sources and producing them by recombinant genetic engineering techniques from mammals, including humans.