The N-myc gene is amplified in several types of human tumors. To assess the role of the N-myc gene in the transformation of normal human cells, we transfected an N-myc expression vector into diploid human fibroblasts. Transfected clones were isolated and found to express the N-myc gene at levels similar to those seen in a tumor cell line (neuroblastoma LA-N-1) which contains an amplified N-myc gene. The level of N-myc expression decreased as the N-myc clones senesced. Clones expressing N-myc had an increased saturation density and an altered morphology but did not have an extended lifespan. Under low serum conditions, neither the clones expressing N-myc nor the control cells showed anchorage-dependent growth. Clones expressing N-myc were compared to control cells to determine if different growth factors would affect the ability of cells to grow in soft agarose. Clones expressing N-myc and the control cells did not grow in soft agarose supplemented with epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha). However, compared to control cells, clones expressing N-myc grew in agarose 2.8- to 18-fold higher in response to basic fibroblast growth factor (bFGF) and 5.5- to 55-fold higher in response to platelet-derived growth factor B-chain homodimer (PDGF-BB).