S-100 protein (S-100p) is a small, acidic, calcium-binding protein that is present (predominantly) in the cytoplasm of many types of cells including those of neuroectodermal origin, such as glial cells, schwann cells and melanocytes. In human melanoma cells S-100p is abundant relative to the small quantities expressed by normal melanocytes. We investigated the possibility that this protein may be a growth factor. Purified S-100p from bovine brain or human melanoma cells was added exogenously to human melanoma cells and peripheral blood lymphocytes (PBL) and their growth in the presence of different concentrations of S-100p was determined using a [3H]dT-uptake proliferation assay. The growth of melanoma cells was stimulated by S-100p at concentrations of 1.95-31.25 micrograms/ml. Slight inhibition of cell proliferation occurred at high concentrations (125 micrograms/ml). Maximum stimulation of PBL was at 31.25 micrograms/ml. PBL were not inhibited even at high concentrations of S-100p (125 micrograms/ml). PBL stimulation by S-100p did not require the presence of monocytes/macrophages. Though stimulation by S-100p is not restricted to a specific cell type, when released by melanoma cells it may function as an "autocrine" tumor growth factor. Other cells, such as PBL, coming in contact with S-100p are also stimulated to proliferate.