The 3' terminus of the single-stranded, negative-sense genome of the measles virus comprises a 55-nucleotide-long sequence, which is transcribed into a short, positive-sense RNA called the leader sequence. In other viral systems, this RNA has been shown to modulate host cell transcription. Here, we report the presence of measles virus leader RNA in both cytoplasmic and nuclear fractions of infected HeLa cells as well as T- and B-lymphoid cells. A sharp and rapid increase in the concentration of leader RNA in the nucleus of infected HeLa cells was also observed. The presence and accumulation of leader RNA in the nucleus of infected cells supports the hypothesis that the leader RNA plays a role in the down regulation of host cell transcription and may be responsible for the suppression of immunoglobulin synthesis by measles virus-infected B cells. Such alterations in immune responsiveness could aid in the establishment of a persistent infection by measles virus.