Recently, selective inhibition of poliovirus b y 2-(a-hydroxybenzyl)-benzimidazole was described (1-3).Following the original report (1) concerning inhibition of poliovirus by 2-(o~-hydroxybenzyl)-benzimidazole (HBB), it was shown in quantitative studies (2, 3) that HBB inhibits the multiplication and the cytopathic effects of poliovirus type 2 in monkey kidney cells, but does not inhibit influenza B virus in the same cell system or in the chorioallantoic membrane from embryouated chicken eggs. At concentrations sufficient to cause marked inhibition of poliovirus, the compound had no effect, or only a slight effect, on the morphologic appearance of monkey kidney cells. Thus, HBB showed significant biological selectivity in its virus in- hibitory action. Inhibition of viral cytopathic effects appeared to be due to inhibition of virus multiplication. It should be emphasized that HBB was virostatic, but not virocidal, for poliovirus.Studies of structure-activity relationships with HBB and related compounds suggested (3) that the hydroxybenzyl grouping at position 2 in the imidazole ring was of fundamental importance for the selective virus inhibitory action of HBB (of. Text- fig. 1). HBB could not readily be considered a close structural analog of any known metabolite. Furthermore, the fact that the compound did not damage cells at virus inhibitory concentrations, made it seem nnlilrely that HBB was acting as an antagonist of a metabolite required by both the host cell and the virus.These findings suggested a new approach to the study of mechanism of virus multiplication: it appeared that with the aid of HBB and related corn-* Aided by a grant from The National Foundation.