We report that the expression of mRNA and the activity of UDP‐glucose:ceramide (Cer) glucosyltransferase‐1 (GlcT‐1) of human hepatoma Huh7 and mouse melanoma B16 cells increases after treatment with bacterial sphingomyelinase or upon addition of short‐chain Cer. Interestingly, however, GlcT‐1 gene transcription was not increased by Cer when GlcT‐1 cDNA was introduced with the CMV promoter in GlcT‐1‐deficient GM95 cells, suggesting that the normal promoter region of GlcT‐1 gene is essential for the response. The conversion of C6‐Cer to C6‐GlcCer occurred much more rapidly in GlcT‐1‐overexpressing Huh7 cells than in mock transfectants. As a result, GlcT‐1‐overexpressing cells acquired a greater resistance to C6‐Cer‐mediated cell death.