Before the prophylactic effect of human interferon alpha 2 (HuIFN-alpha 2) can be tested against naturally acquired rhinovirus infection in a large-scale field trial, it is desirable to show that self-administration of the drug is practical, and to determine the smallest well-tolerated dose likely to produce a worthwhile effect. Here we report that self-administered intranasal interferon can be effective, and show how prophylaxis against rhinovirus infection is affected by both the quantity of interferon, and the interval between a dose and virus challenge. Finally, the medication regimen suggested for use in field trials (3.85 MU 3 times/day) was tested in a double-blind, placebo-controlled trial in volunteers. Although virus challenge was at a time when those being treated with interferon would be most susceptible, a substantial protective effect was still demonstrated.