A plot of the uptake rate of thymine by H. diminuta was sigmoidal, indicating an allosteric activation of the transport rate. Thymine also stimulated the uptake of uracil, and a Hill plot of these data had a slope of 1.2, suggesting that there are at least 2 binding sites on the purine-pyrimidine permease. From the effects of various pyrimidine analogs on uracil transport, it was concluded that the addition of a methyl group on carbon 5 of uracil gave a structure that caused more activaticn than 5-amino or 5-bromo groups; when the methyl group was on carbon 6 of uracil, the structure caused inhibition of uracil transport. No effect on uracil transport was observed in the presence of 5-hydroxymethyluracil or 5-carboxyuracil. A plot of the uptake rate of uridine gave typical saturation kinetics, but the presence of thymine stimulated uridine transport. Attempts to show exchange of uracil for other base analogs were negative. Activation of pyrimidine transport by thymine may provide a way to increase permeability of analogs that are effective inhibitors of nucleic acid synthesis. Maclnnis, Fisher, and Read (1965) reported that thymine stimulated uracil transport by Hymenolepis diminuta, and that the locus for mediated transport of purines and pyrimidines was separate from the sites for mediated transport of amino acids and sugars. Since most other purine or pyrimidine analogs inhibited uracil transport, the stimulation by thymine was unexpected. Other experiments (MacInnis et al., 1965) showed that the stimulatory effect of thymine could be modified by the simultaneous presence of an inhibitor such as hypoxanthine, indicating an apparent competitive inhibition or stimulation. This modulation might occur at the surface of the worm by affecting the permease (or carrier) molecules (Wong, 1965). Kammen (1967) concluded that the presence of purine deoxyribonucleosides enhanced the uptake and utilization of thymine by Escherichia coli. However, little information is available on the mechanisms of such regulations occurring on outer cell surfaces, although allosteric regulations are common within cells (Atkinson et al., 1965; Stein, 1967). Potentiation of pyrimidine transport by thymine may provide a way to increase permeReceived for publication 1 July 1969. * This study was supported by NSF GB 5167, the University of California Research Grant 2280, and NIH AI00070. t NIH Postdoctoral trainee (AI00070). Present address: Department of Infectious Diseases, Kansas State University, Manhattan, Kansas 66502. ability of analogs that are not normally transported by parasites, but that are effective inhibitors of nucleic acid synthesis. We herein report further investigations on the regulatory effect of thymine and thymine analogs on the uptake of uracil and other bases and ribosides. These experiments were designed to determine the molecular configuration of the pyrimidine that activates the transport rate, and the mechanism of the activation. MATERIALS AND METHODS Male albino rats (Sprague-Dawley, UCLA Life Sciences Vivarium Strain) weighing 100 to 150 g were each infected with 30 cysticercoids of Hymenolepis diminuta (Rice University Strain) obtained from infected Tribolium confusum using the technique of Ridley and Maclnnis (1968). Worm preparations and incubations followed the procedures standardized by Read, Rothman, and Simmons (1963). Minor modifications of experimental techniques are described in context. The uptake data are based on the amount of radioactive material extracted into 70% ethanol, then converted to ,moles/g/hr of the ethanolextracted dry weight by appropriate standards and calculations. 1Carbon labeled isotopes were used in all experiments. Labeled uracil, uridine, thymine, guanine, isoleucine, and phenylalanine were obtained from New England Nuclear Corp. 14C-glucose was obtained from Calbiochem Corp. Labeled thymidine (deoxyribose) and uridine (ribose) were obtained from both of the above companies. Purine bases and ribosides were labeled in the 8 position; pyrimidine bases and ribosides were labeled in the 2 position; the amino acids and glucose were uniformly labeled. Uracil-5-carboxylic acid, 6-methyluracil, and 5-