We have developed a new system suitable for easy inexpensive screening of substances potentially active against HIV and other retroviruses. The system evaluates the ability of substances to inhibit the high-frequency induced retrotransposition of the yeast transposable element Ty917, and is based on an engineered version of the retrotransposon which carries a dominant selectable marker useful for scoring transposition events. The system performance was evaluated using two nucleoside analogues of proved anti-HIV activity, 3'-azido-3'deoxythymidine (AZT) and 2',3'-dideoxycytidine (ddC). Both substances were able to inhibit Ty917 transposition and could have been detected as potentially active antiretroviral drugs using the new screening system.