The 1-O-octadecyl 2-O-methyl-sn-glycerophosphocholine (ET-18-O-CH3), when incubated for 24-48h with cells in culture, exerts a highly selective cytotonic activity against a variety of tumor cells that is not seen in normal ones. In this study, we present data which indicate that this exogenous molecule altered the endogenous synthesis of the neutral ether, ester-sn-glycerols, in 2 variant cell lines of a rat colon carcinoma. ET-18-O-CH3, at 20 microM in the medium and for an incubation of 48h, inhibited the growth rates of the PRO cells which have the ability to metastasize and of the REG cells (the regressive cell line), by, respectively, 54 and 67%, as measured after [3H] thymidine uptakes. The synthesis of the ether, ester-glycerolipids was followed after an incorporation of [3H] hexadecanol into the cell lipids. The radiospecific activity of the alcohol in the ether, ester-glycerolipids was higher for the PRO cells than for the REG cells. ET-18-O-CH3 activated the incorporation of [3H] hexadecanol in the neutral ether, ester-sn-glycerols: 1.55 fold in the PRO cells, but 2.15 fold in the REG cells. No change was observed in the alkyl (alkenyl) acyl-sn-glycerophospholipids. Most of the transformed cells have a low etherase activity and are known to accumulate the ether, ester-glycerolipids, (neutral and ionic structures).(ABSTRACT TRUNCATED AT 250 WORDS)