The effect of the acyclic nucleotide analogue, 9-(2-phosphonomethoxyethyl)adenine (PMEA, Adefovir), and its (bis)pivaloyloxymethyl ester (bis-POM-PMEA, Adefovir Dipivoxil) on in vitro nitric oxide (NO) production by murine peritoneal macrophages was investigated. Bis-POM-PMEA inhibited in a concentration-dependent manner the formation of NO generated by interferon-γ and lipopolysaccharide, the IC 5 0 being 15 μM. Suppressed transcription of mRNA for inducible NO synthase (EC 1.14.13.39) resulting in decreased synthesis of NO synthase protein was found. Parent compound PMEA was virtually ineffective.