Stavudine, a potent antiviral agent for treating human immunodeficiency virus (HIV) infections, was radiolabeled with (11)C by methylation of a specifically designed precursor, 5'-O-(2-tetrahydropyranyl)-5-bromo-2',3'-didehydro-3'-deoxythymidine, with (11)C H(3)I. The radiolabeled drug was isolated by reverse phase HPLC. A total time of approximately 45 minutes was required for synthesis, purification and isolation of (11)C stavudine with chemical and radiochemical purities of greater than 98%. (11)C stavudine was combined with unlabeled drug (2.0 mg/kg) and used to study its pharmacokinetics in rats by measurement of radioactivity in excised tissues. In this species, there was rapid accumulation of drug in all tissue. In all tissues, with the exceptions of testis and brain, highest concentrations of drug were detected at 5 minutes after injection and decreased monotonically thereafter. The peak concentration (microg/g) of stavudine in blood was 1.78 +/- 0.16 and similar levels were achieved in most other tissues; heart 1.66 +/- 0.11, lung 1.60 +/- 0.15, liver 2.13 +/- 0.17, spleen 1.61 +/- 0.15, adrenal 1.47 +/- 0.20, stomach 1.40 +/- 0.11, GI tract 1.44 +/- 0.14, skeletal muscle 1.38 +/- 0.15 and bone 1.30 +/- 0.16. Much higher peak concentrations were achieved in kidney; 7.23 +/- 0.57 microg/g. Concentrations in testis were lower and remained relatively constant over 1 hour; peak 0.62 +/- 0.14 microg/g at 15 min Brain concentrations were low but increased monotonically over time; peak 0.26 +/- 0.02 microg/g at 60 min. Future PET studies with this radiopharmaceutical will allow in vivo measurements of the pharmacokinetics of stavudine in both animal models and human subjects.