AbstractOne approach to the problem of growth factor signal transduction is to identify alterations in growth factor-regulated events in mutants possessing an altered proliferative response. This approach was used in a study of the alterations in protein tyrosine phosphorylation in 22 independently-arising autonomous mutants of the CSF-1-dependent mouse macrophage cell line, BACl.2F5. Only 4 of the mutants produced CSF-1 and/or factors that were capable of down-regulating the CSF-1 receptor (CSF-1R), suggesting that the majority were altered in the signal tranduction pathway for proliferation. All of the mutants possessed lower numbers (13-89%) of cell surface CSF-1Rs than wild type cells. With two possible exceptions, the phosphorylation of the anti-phosphotyrosine-reactive cell surface CSF-1 Rs from CSF-1 stimulated cells was directly proportional to cell surface CSF-I R number. In the absence of CSF-I, three of the 22 mutants exhibited tyrosine phosphorylation of proteins that was not observed in wild type cells under the same conditions. The results indicate that this approach will be useful in the analysis of the growth factor regulated pathway for cell proliferation.