The C protein of human parainfluenza virus type 3 (HPIV 3), like other paramyxovirus C proteins, is synthesized from an alternate open reading frame (ORF) encoded within the phosphoprotein (P) mRNA, in addition, to two other proteins, namely D and V, which arise from the same mRNA by a process of transcriptional editing. The precise role of the C, D, and V proteins in viral transcription and replication, and their interaction, if any, with other viral proteins remains unknown. To ascertain the role of the C protein, we have examined its effect on transcription using an HPIV 3 minigenome construct and monitoring the luciferase reporter gene expression. Our results demonstrate that the HPIV 3 C protein effectively inhibits minigenome transcription in a dose-dependent manner. Interestingly, the Sendai virus (Se-V) C protein was also capable of inducing an inhibitory effect on the HPIV 3 minigenome transcription, thus demonstrating a heterologous interaction. A coiled-coil motif within the C protein has been identified, and a deletion mutant within this motif abrogated the inhibitory effect significantly thereby implying that oligomerization of the C protein may be involved in inhibition of transcription.