In a five-week double-blind trial, 132 young adult volunteers received U.K. 2371, a synthetic isoquinoline derivative which had previously been shown to protect volunteers against challenge with certain influenza viruses. A comparable group of 130 volunteers received placebo. There was little difference between the groups in number or severity of acute respiratory illnesses during the trial or in the number of proven infections with influenza A2/Hong Kong/1968 virus. Tablet counts were carried out and single doses of isoniazid were used as a marker to confirm that the lack of prophylaxis was not the result of the failure of volunteers to ingest the tablets. It is possible that the disparity between our results and those obtained in previous volunteer challenge studies may be due to differences in susceptibility of strains of influenza A virus to the isoquinoline drugs.