Suramin is a polysulfonated naphthylurea currently investigated for the treatment of advanced malignancy. We have previously reported that suramin was a potent inducer of the differentiation of the human colic adenocarcinoma cell clone HT29-D4 (Fantini et al., J Biol Chem, 1989; 264: 10282-10286). In this report, we show that chronic suramin treatment of these cells is associated with a lysosomal storage disease. We have tested five suramin-related compounds for their ability to induce HT29-D4 differentiation and we looked at their action on the lysosomal apparatus. We conclude that one of the derivatives used is a more potent differentiation inducer than suramin, while it does not elicit any perturbation of the lysosomal system.