The pharmacokinetics of 3-deazaneplanocin A (c3Nep), a competitive inhibitor of S-adenosyl-L-homocysteine (AdoHcy) hydrolase and novel antiviral agent, was investigated in female BALB/c mice. Animals were given a single intravenous dose of [3H]-c3Nep (0.1 mg/kg; 10 microCi), and blood and selected tissues were collected at various intervals thereafter for up to 72 h. The plasma concentration versus time data for c3Nep was best approximated by a two-compartment open model with first order elimination. The elimination half-life was 12.8 min, the area-under curve (AUC) was 3.38 micrograms.min.ml-1. The distribution of c3Nep into tissues was not extensive. Following 30, 120 min, and 24 h after dosing, the kidneys and the liver contained the highest amount of drug, but this amount did not exceed 1 microgram/g tissue. At these time periods, the majority of activity in the tissues represented labeled derivatives of c3Nep indicating that this compound was converted to stable metabolites. The presence of labeled conversion products in the blood confirmed that this drug is metabolized in vivo. The fact that c3Nep bound to plasma proteins in vitro may explain this drug's limited tissue distribution. The half-life and tissue distribution of c3Nep were different from those of carbocyclic 3-deazaadenosine, a related adenosine nucleoside antiviral drug and AdoHcy hydrolase inhibitor.