We have previously demonstrated that over-expression of c-myc facilitates the replication of SV40 DNA in human Burkitt lymphoma cells (BL). In this paper we investigated the ability of N-myc and L-myc to substitute for c-myc in promoting SV40 DNA replication. Vectors expressing either a chimeric N-myc/c-myc, N-myc or L-myc gene were constructed and co-transfected with a plasmid containing the SV40 origin of replication and the early genes encoding SV40 T antigens (Tag). The chimeric N-myc/c-myc and the N-myc proteins enhance SV40 replication in the human lymphoma line BJAB at levels comparable to c-myc. The stimulative effect of N-myc is also evident in the BL cell line RAMOS. However, L-myc stimulated SV40 replication only in RAMOS cells.