A wide variety of purine nucleoside (mainly tubercidin and adenosine) analogs, which had previously been shown to inhibit the replication of a broad spectrum of RNA viruses, were evaluated for their antirhinovirus activity in human diploid (WI-38) fibroblasts. Tubercidin, 5-(1-hydroxyethyl)tubercidin, 5-(2-buten-1-yl)tubercidin, toyocamycin, and sangivamycin emerged as the most potent inhibitors. These compounds inhibited the replication of rhinovirus types 1A, 1B, and 9 at an MIC well below 1 microgram/ml. However, these compounds proved cytotoxic for the uninfected host cells at concentrations which were only slightly higher (3- to 10-fold, on the average) than those required for inhibition of rhinovirus replication. The most selective inhibitor of rhinovirus replication was 3-deazaguanine, with a selectivity index of 50. None of the carbocyclic and acyclic analogs of adenosine tested exhibited a potent or selective antirhinovirus activity.