The growth responses of hamster dermal fibroblasts (HDF cells) to platelet-derived growth factor (PDGF) during chemical carcinogenesis in vitro were investigated. Normal HDF cell grew in medium with whole blood serum (WBS), but not in medium with plasma-derived serum (PDS). However, they grew in PDS medium when PDGF was added. In contrast to control cultures which finally stopped proliferating, 7 out of 8 cell strains treated with 4-nitroquinoline-1-oxide (4NQO) or N-methyl-N'-nitro-nitrosoguanidine changed to cell lines. Later, 5 of these 7 cell lines became able to grow in PDS medium in association with ability to grow in soft agar. When clonal cell lines were isolated at early stages of carcinogenesis while parental cell lines were still PDGF-dependent, most of them gradually became PDGF-independent as well. Dialysed cell lysates of transformed HDF cells showed strong growth stimulating activity on normal HDF cells in PDS medium. Thus, this conversion of PDGF-dependent cells to PDGF-independent cells was correlated with the appearance of a growth factor(s) produced specifically by transformed HDF cells.