Novel inhibitors of histidinol dehydrogenase are described. The most potent inhibitors, compounds 18 (K i• = 4.4 nM) and 19 (K i• = 2.9 nM) exploit a hitherto unreported lipophilic binding pocket adjoining the active site. Preliminary SAR data for this pocket are detailed. The electrophilic ketone 6 designed to bind to an active site nucteophile was a considerably weaker inhibitor (ICs0 -201aM).