The functional changes of cytoplasmic membrane of mammalian cells as an alternative approach for evaluating the tumor promoter activity were investigated. The V79 metabolic cooperation assay, as the standard method for detection of tumor promoters in vitro was used. From three known tumor promoters only phenobarbital increased the efflux of [3H]2-deoxy-D-glucose-6-phosphate from the cells in the same concentration range where the inhibition of metabolic cooperation was estimated. Neither TPA, saccharin nor theophylline caused any functional changes of cytoplasmic membrane of V79 cells. On the basis of the results with known tumor promoters we suggest that following the functional changes of cytoplasmic membrane is not a convenient approach for screening potential tumor promoters.