A total of 17 monensin urethanes, including two naturally produced phen-ethylurethanes (Streptomyces sp.), were evaluated for antiparasitic activity. All of the compounds had the characteristic properties of the polyether antibiotics including their ability to transport cations across membranes. Several of the semisynthetic derivatives demonstrated in vitro and in vivo anticoccidial activity in chickens. In vitro activity was shown utilizing chick kidney cell culture experimental procedures in which several of the semisynthetic antibiotics were active at 1 ppm or less. Derivatives having anticoccidial efficacy exhibited activity in vitro against Treponema hyodysenteriae, the causative agent of swine dysentery. Mice previously treated with specific semisynthetic urethanes survived a severe Plasmodium berghei challenge indicative of antimalarial properties as well. Specific biological activity could be correlated with structural relationships of the semisynthetic urethanes.