Interferon induction in BSC-1 cells by measles virus isolates previously found to be interferon inducing (IF+) or interferon noninducing (IF-) was studied in different cell types. Lack of induction by the IF- viruses was not due to an inhibitory factor since BSC-1 cells coinfected with IF+ and IF- stocks produced interferon levels similar to those infected with IF+ stocks alone. Various tests indicated that the phenotypic expression of interferon induction by these isolates was dependent on an infectious virus genome, the cell type tested, and the passage history of the virus. In contrast to the in vitro results, the IF- phenotype was stable in vivo, whereas passage of the IF+ virus resulted in selection against the IF+ phenotype. The phenotypic expression of interferon induction by measles virus was, therefore, controlled by complex interactions between virus and host cell factors exerted both in vivo and in vitro.