Toward the goal of gene therapy, we have been attempting to establish model somatic cell systems with the potential of sustained expression of the foreign gene. We report here that long-term expression of foreign genes in mouse embryo fibroblast implants can be achieved if a housekeeping gene promoter is used to drive transcription. Specifically, we have shown that in implants containing a beta-galactosidase gene linked to either an immediate early promoter of cytomegalovirus or a dihydrofolate reductase (DHFR) gene promoter, only the DHFR promoter allows long-term expression. We propose that choice of the promoter manifests significant influence on the long-term expression of genes introduced in fibroblast implants by retroviral vectors.