BHK-21 cells persistently infected with either vaccinia or foot and mouth disease virus were used to study the efficacy of antiviral compounds. The results of the persistent infection cell culture (PICC) test were compared with those obtained by the plaque reduction (PR) test. The comparison showed that: (1) the PICC test is more informative than the PR test; (2) stimulative as well as inhibitory activities of compounds are detectable, and (3) since the PICC test can be carried on for several weeks or even months this test is especially well suited to study the problem of drug resistance in cell cultures.