Human cytomegalovirus induced beta interferon in cultures of human foreskin cells. The inhibitor was first released between 8 and 16 hours after infection, about 48 hours before progeny virus. In cultures infected with low concentrations of virus, interferon was produced as the infection spread, and then in amounts larger than expected. After infection with cytomegalovirus, cells which had been primed for 48 hours with purified beta interferon produced significantly more interferon than unprimed cells, and the interferon was produced earlier, between 2 and 8 hours after infection. CMV-induced interferon also was able to prime cells. The data suggest that the relatively large quantities of interferon detected in cultures infected with low concentrations of cytomegalovirus result from endogenous priming: those cells infected early first produce interferon which primes uninfected cells, then virus which induces the primed cells to produce interferon in relatively high concentrations.