Six rhinovirus serotypes showed in vitro susceptibility to two analogues (SK&F 21687 and SK&F 30097) of 3-substituted triazinoindole compounds. The intranasal SK&F 21687 medication did not prevent upper respiratory illness in 10 men who were challenged with rhinovirus type 44. No differences in the frequency and severity of clinical illness, virus shedding patterns, and serum and respiratory secretory antibody responses were detected between these drug-treated men and 10 placebo control subjects. The failure to affect the course of the illness may have been due to the insolubility of the test drug. Development of drug resistance by the virus was not demonstrated during the topical medication and the in vitro test.